PYRIMIDINE DERIVATIVES This invention relates to pyrimidine derivatives and to processes for the preparation of, compositions containing and the uses of, such derivatives. The pyrimidine derivatives of the present invention are histamine H4 receptor ligands and have therefore a number of therapeutic applications, particularly in the treatment of asthma, allergic rhinitis, chronic obstructive pulmonary disorder (COPD) and histamin6-mediated inflammatory diseases. The histamine H4 receptor is a 390 amino-acid, seven-transmembrane G protein coupled receptor with approximately 40 % homology to the histamine H3 receptor, (n contrast to the H3 receptor, which is primarily located in the brain, the H4 receptor is expressed at greater levels in eosinophils and mast cells, among other inflammatory ceils. H4 receptor ligands should thus be suitable for the treatment of various inflammatory disorders. Examples of diseases where treatment with H4 ligands is particularly appropriate are inflammatory bowel disease, Crohn''s disease, colitis µLcerosa, dermatitis, psoriasis, conjunctivitis, rheumatoid arthritis, respiratory diseases such as adult respiratory distress syndrome, acute respiratory distress syndrome, bronchitis, chronic bronchitis, chronic obstructive pulmonary disease, cystic fibrosis, asthma, emphysema, rhinitis, chronic sinusitis, allergy, allergy-induced airway responses, allergic rhinitis, viral rhinitis, non-allergic rhinitis, perennial and seasonal rhinitis, nasal congestion and allergic congestion. Recently some histamine H4 receptor ligands have been developed. An overview of the current advance in H4 ligand research and patenting is given in Expert Opin. Ther. Patents {2003) 13(6). Examples of Histamine H4 receptor ligands can be found in WO 02/072548, WO 04/022537 and in Terziogiu et al., J. Bioorg. Med. Chem Lett. 14 (2004), 5251-5256. Although H4 ligands are known there is still a need to further provide new H4 ligands that are good drug candidates. In particular, preferred compounds should bind potently to the histamine H4 receptor whilst showing little Nfinity for other receptors. They should be well absorbed from the gastrointestinal tract, be metabolically stable and possess favourable pharmacokinetic properties. They should be non-toxic and demonstrate few sid6-effects. The present invention thus relates to pyrimidine derivatives of formula (I): (Formula Removed) 2 or a pharmaceutically and/or veterinarlly acceptable derivative thereof, wherein: R1 is C1-8alkyl, C3-7cycloalkyl-C0-6alkyl- optionally substituted with methyl, alkoxyalkyl containing 3 to 8 carbon atoms, het-C0-6alkyl-, CF3-C1-6alkyl-, CF3OC2-3alkyt-, aryl-C0-6alkyl- orC1-6''hydroxyalkyl; R2 is het, provided that the net group contains at least one nitrogen atom or is substituted by a group which contains at least one nitrogen atom; or R2 is NH(CH2)2NH2, NH(CH2)2NHCH3, or NH(CH2)2NH{CH3)2, R3 is H, C1-8alkyl, (CH2)pC3-7cydoaIkyt, alkoxyalkyl containing 3 to 8 carbon atoms, {CH2)nCF3l {CH2)xOCF3 or C1-6hydroxyalkyl; or R3 and R2 together with the nitrogen atom to which they are bound form a 4 to 8 membered non-aromatic heterocyclic group which optionally contains one or more further fieteroatoms or groups independently selected from N, O, S, S(O) and S(O)2, wherein the heterocyclic group is optionally a bridged bicyclic group, a spiro bicyclic group or is optionally fused to a 3-, 4-, 5- or 6-membered carbocydic group or a 4-, 5- or 6-membered heterocyclic group which contains at least one ring member independently selected from N, O, S, S(O) and S(O)2, and wherein the ring system as a whole Is optionally substituted by one or more substituents independently selected from C1-6alkyl, NRBR7, (CH2)aC3-7cycloalkyl, alkoxyalkyl containing 2 to 8 carbon atoms, (CH2)bhet\ (CH2)CCF3, (CH2)yl)CF3, (CH2)daryl and Ci.shydroxyalkyl, provided that the ring system as a whole contains at least two nitrogen atoms or contains one nitrogen atom and is substituted by a group which contains at least one nitrogen atom; R4 is H; or R1 and R4 together with the nitrogen atom to which they are bound form a 4 to B membered non-aromatic heterocyclic group which optionally contains one or more further heteroatoms or groups independently selected from N, O, S, S(O) and S{0)2l wherein the heterocyclic group is optionally a bridged bicyclic group or is optionally fused to a 3-, 4-, 5- or 6- membered carbocydic group or a 4-, 5- or 6-membered heterocyclic group which contains at least one ring member independently selected from N, O, S, S(O) and S(O)2, and wherein the ring system as a whole is optionally substituted by one or more substituents independently selected from C1-6alkyl, fluoro, NR9R10, {CH2)eC3-7cycloalkyl, alkoxyalkyl containing 2 to 8 carbon atoms, {CH2)|het; (CH2)gCF3, (CH2)zOCF3, (CH2)haryl and C1-6hydroxyalkyl; R5 is H or NR11R12; R6 and R7 are each independently selected from H, C1-6alkyl and (CH2)C3-7cycloalkyl; or R8 and R'''', together with the nitrogen atom to which they are bound, form a 4, 5 or 6 membered heterocyclic group; R8 is H or C1-3alkyl; R9 and R10 are each independently selected.from H, Cvsalkyl and (CH2)kC3-7cyctoalkyl; or R5 and R10, together with the nitrogen atom to which they are bound, form a 4, 5 or 6 membered heterocyclic group; R11 and R12 are each independently selected from H, C1-6alkyl and (CH2)tC3-7cycloaikyl; or R11 and R12, together with the nitrogen-atom to which they are bound, form a 4, 5 or 6 membered heterocyclic group; R13 and R14 are each independently selected from H, C1-6alkyl and (CH2mCl2cycloalkyl; or Rtt and R14, together with the nitrogen atom to which they are bound, form a 4, 5 or 6 membered heterocyciic group; a, b, c, d, e, f, g, h, j, k, I, m and p are each independently selected from 0, 1,2 and 3; n is 1, 2 or 3; x is 2 or 3, wherein If x Is 3, then the (CH2)3 group may be replaced with a branched alkyl group containing 3 carbon atoms; y and z are each independently selected from 1, 2 and 3 aryl is phenyl, naplithyl, anthracyl or phenanthryl, each optionally substituted by one or more groups independently selected from C1-8alkyl, C1-8alkoxy, OH, halo, CF3, CHF2, OCF3l. OCHF2, SCF3| hydroxy-C,. 6alkyl, C1-4alkoxy-C1-6-Balkyl, C1-4alkyl-6-GMalkyl, aryl1, het1, Oaryl1, Ohet'', Saryl1, Shet1, CF2CFa, CH2CF3, CF2CH3, C(O)NR13R14, C3-8cycloalkyl, C3.7cyclaalkyl-C1-4alkyl, C3-7cyctaaIkyl-&Malkoxy, C3-7cyctoalkyl-O-C1-4alkyl, C3-7cycloalkyl-C1-4alkoxy-C1-4alkyl, OC3-7cycloalkyl and SC3-7cycloaJkyl, wherein the aryl1 and het1 groups are optionally substituted by at least one group selected from C1-Salkyl, C3.7cycloalkyl, C,_ 6alkoxy, OCvFcycloalkyt, halo, CN, OH, CF3, CHF2, OCF3, OCHF2, hydroxyC^aikyl, CMaI.koxy-C1-4alkyl, SC1-6alkyl and SCF3; het is 4 to 8 membered non-aromatic heterocyclic group which contains at least one heteroatom or group independently selected from N, O, S, S(O) and S(O)2, wherein the heterocyclic group is optionally a bridged bicyclic group or is optionally fused to a 3-, 4-, 5- or 6- membered carbocydic group or a 4-, 5- or 6-membered heterocyclic group which contains at least one ring member independently selected from N, O, S, S(O) and S(O)2l and wherein the ring system as a whole is optionally substituted by one or more substituents independently selected from d-ealkyl, NR6R7, (CH2)aC3-7cydoalkyl, alkoxyalkyl containing 2 to 8 carbon atoms, (CH2)bhet1, (CH2}cCF3, (CH2)yl)CF3, (CH2)daryl and C1-6hydroxyalkyl; aryl1 is phenyl, naphfhyl, anthracyl or phenanthryl; and het1 is an aromatic or non-aromatic 4-, 5- or 6- membered heterocycle which contains at least one N, O or S heteroatom, optionally fused to a 4-, 5- or 6- membered carbocydic group or a second 4-, 5- or 6-membered heterocycle which contains at least one N, O or S heteroatom. Preferably aryl is phenyl. For embodiments in which the groups "aryl", "aryl1", "het" and "het1° may be a substituent on more than one part of the compound, it is to be understood that each separate substituent may be the same or different to the other substituent{s) defined by the same term. For example, if R1 and R2 both comprise a "het" group, then the two het groups may be the same or different. It has been found that the compounds defined above are Ifgands of the Histamine H4 receptor. In an embodiment of the invention R1, R2, R3, R4 and R5 are as defined above, and R8 is hydrogen. In a further embodiment, R1, Rz, R3, R5 and R3 are as defined above, and R4 is hydrogen. In a further embodiment, R2, R3, R6 and R8 are as defined above, R4 is hydrogen and R1 is C3-7cydoalkyl- C0-6alkyl- optionally substituted with methyl. In a further embodiment, Rz, R3, R5 and R8 are as defined above, R4 is hydrogen and R1 is C3-5cycloalkyl- C0-1alkyl- optionally substituted with methyl. In a further embodiment, R2, R3, R5 and RB are as defined above, R4 is hydrogen and R1 is cyclopropyl, cyclopropyl-methyl or methyl-cyclopropyl. In a further embodiment, R2, R3, R5 and R8 are as defined above, R4 is hydrogen and R1 is C1-C6 aikyl. In a further embodiment, R2, R3, R5 and R8 are as defined above, R4 is hydrogen and R1 is C1-C6 aikyl. In a further embodiment, R2, R3, R5 and R8 are as defined above, R4 is hydrogen and R1 is ethyl, propyl, butyl, 1-methyl-propyl, 2-methyl-propyl, 2,2-dimethyl-propyl, 2-methyl-butyl, ter-butyl, 1-methyl-butyl, 3- methyl-butyl, 3,3-climethyl-butyl, 1,2-dimethyl-propyl or isopropyl. In a further embodiment, R1, R4, R5, and R8 are as defined above, and R2 is liet, provided that the het group contains at ieast one nitrogen atom or is substituted by a group whicli contains at least one nitrogen atom and R'' is H, Ci.eallcyl, (CH2)pC3-7cydoalkyl, alkoxyallcyl containing 3 to 8 carbon atoms, (CH2)nCF3, (CH2)xOCF3 or C,.Bliydn3xyaikyl; or R3 and R2 together with the nitrogen atom to whih they are bound form a 4 to 8 membered non-aromatic heterocydic group whfch optionaJly contains one or more further ineteroatoms or groups independently seiected from N, O, S, S(O) and S(O)2, wherein the heterocyclic group is optionaliy a bridged bicyclic group, a spiro btcydic group or is optionaily fused to a 3-, 4-, 5- or 6- membered carbocyclic group or a 4-, 5- or e-membered heterocyclic group which contains at least one ring member independently selected from N, O, S, S(O) and S(O)2, and wherein the ring system as a whole is optionaliy substituted by one or more substituents independently selected from C1-6allatic hetenscycitc group which optionally contains one or more further heteroatoms or gnaups independently selected fromi N, O, S, S(O) and S(0}2, wherein the heterocyclic group is optionally a bridged blq/clic group or is optionally fused to a 3-, 4-, 5- or 6- membered carbocyclic group or a 4-, 5- or 6-membered heterocyclic group which contains at least one ring member independently selected from N, O, S, S(O) and S(O)2, and wherein the ring system as a whole is optionally substituted by one or more substituents independently selected from C1. 6aikyl, NR6R7, {CH2)aC3-7cycloalkyl, alkoxyalkyi containing 2 to 8 carbon atoms, (CH2)bhet1 (CH2)cCF3, (CH2)yOCF3, (CH2)daryl and C1-6hydnaxyalkyI, provided that the ring system as a whole contains at least two nitrogen atoms or contains one nitrogen atom and is substituted by a group which contains at least one nitrogen atom. In a further embodiment, R1 R4, R5 and R8 are as defined above, and R2 and R3 together with the nitrogen atom to which they are bound, fomi a 4 to 8 membered non-aromatic heterocyclic group which optionally contains one or more further nitrogen atoms, wherein the heterocyclic group is optionally a bridged bicyclic group or is optionally fused to a 3-, 4-, 5- or 6- membered carbocyclic group or a 4-, 5- or 6-membered heterocyclic group which contains at least one nitrogen atom, and wherein the ring.system as a whole is optionally substituted by one or more sulsstituents independently selected from C1-6eaikyl, NR6R7 {CH2)aC3-7cycloalkyi, alkoxyalkyi containing 2 to 8 carbon atoms, (CH2)bhet'', (CH2)cCF3, (CH2)yOCF3, (CH2)daryl and Ci-ghydroxyalkyl, provided that the ring system as a whofe contains at least two nitrogen atoms or contains one nitrogen atom and is substituted by a group which contains at least one nitrogen atom. in a yet still further embodiment. R1 R4, R5 and R8 are as defined above, and R2 is NH(CH2)2NH2, NH(CH2)2NHCH3, NH(CH2)2NH(CH3)2 and R3 is H, In a yet still further embodiment, R1, R4, R5 and R8 are as defined above, and R2 and R3, together with the nitrogen atom to which they are bound, form a 4 to 8 membered non-aromatic heterocydic group selected from the following ring systems: (Formula Removed) wherein the ring system as a whole may be substituted by one or more C1-6alkyl or (CH2}aC3-6cycloalkyl groups. In a yet still further embodiment, R1, R4, R5 and Ra are as defined above, and Rz and R3, together with the nitrogen atom to which they are bound, form a A to 8 membered non-aromatic heterocyclic group selected from the following ring systems: (Formula Removed) wherein R6 and R7 are independently selected from H or CH5. In a further embodiment, R1, R4, R5 and RB are as defined above, R3 is H and R2 is a pynrolidinyi group, optionally substituted by one or more substituents independently selected from C1-6alky), NR6R7, (CH2)aC3.7cycloalkyl, atkoxyalkyl containing 2 to 8 carbon atoms, (CH2)bhet\ (CH2)cCF3, (CHaJyl)CFa, (CH2)daryl and C1-6hydroxyalkyl. In a further embodiment, R1, R4, R6 and R8 are as defined above, R3 is H and R2 is a pyrrolidinyl group, optionally substituted by one or more substituents independently selected from C1-6alky], NR8R7, (CH2)aC3.7cycloaIkyl and alkoxyalkyl containing 2 to 8 carbon atoms. In a further embodiment, R1R2, R3, R4 and RB are as defined above, and R5 is H or NH2. In the here above formula "halo" denotes a halogen atom selected from the group consisting of fluoro, chloro, bromo and iodo, in particular fluoro or chloro. The term "alkyl" includes both straight-chain and branched chain groups. This also applies if they carry substituents such as a hydroxy substitutent or occur as substituents of other radicals, for example alkoxy groups. For example, the term C1-6alkyl includes methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl and tert-buty! moieties. Examples of the corresponding alkoxy moieties are methoxy, ethoxy, n-propyloxy, rso-propyloxy, n-butyloxy, iso-butyloxy, sec-butyloxy and tret-butyloxy. Furthermore, examples of suitable C1-6alkyl moieties substituted by an hydroxyl group are hydroxymethyl, 1-hydroxyethyll, 2-hydroxyethyl, 1-hydroxypropyl, 2-hydroxypropyl, 3-hydroxypropyl, etc. The term C3-C7 cycloalkyl includes bridged bicyclic cycloalkyl such as bicyclo[1.l1]pentyl. Preferred cycloalkyl groups are cyclopropyl, cyclobutyi, cyclopentyJ, cyclohexyl and bicyclo[1.1.1]pentyl. Preferred "4 to 8 membered heterocyclic group which optionally contains one or more further heteroatoms or groups independently selected from N, O, S, 5(O) and S(O)2, wherein the heterocyclic group is a spiro bicyclic group" are 2,8-diaz3-8plro[4.5]dec-2-yl and 2,7-diaz3-8piro[4.4]non-2-yl. The skilled person will of course appreciate that it is not possible to substitute some of the defined heterocyclic ring groups of Formula 1 in all positions with some of the optional substituents defined above. It is to be understood that such substitutions do not form part of the invention. Example compounds that fail within the above definition of the invention include: N-{3,3-Dimethylbut/])-6-(4-methylpiperazin-1-yI)pyrimidin-4-amine, 6-[3-{Dimethylamino)pyrrolidin-1-yl]-N-(3,3-d''imethy.lbutyl)pyrimidin-4-amine, N-(3l3-Dimethylbut/l)-6-[{3-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl3pyrimidin-4-amine, 6-[3-(Dimethylamino)azetidin-1-yl]-N-(3,3-dimethylbutyl)pyrimidin-4-amine, N-(3,3-Dimethylbutyl)-6-[5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl]pyrimidin-4-amine, N-(3,3-Dimethylbutyl)-N-[pyrrolidin-3-yl]pyrimidin6-4,6-diamine, N-(3,3-Dimethylbutyl)-N-[1-methylpyrrolidin-3-yl]pyrimidin6-4,6-diamine, N4-(Cyclopropylmethyl)-6-[3-(methylamino)pyrrolidin-1-yl]pyrimidin6-2,4-diamine, N4-lsobutyl-6-[3-(methylamino)pyrrolidin-1-yl]pyrimidin6-2,4-diamine, N4-(2,2-Dimethylpropyl)-6-[3-(methylarriino)pyrrolidin-1-yl]pyrimidin6-2,4-diamine, N4-Ethyl-6-[3-(methylamino}pyrrolidin-1-yl]pyrimidin6-2,4-diamine, N-Ethyl-6-[3-(methy)amino)pyrrolidin-1-yl]pyrimidin-4-amine, N-lsobutyl-6-[3-(methylamino)pyrrolidin-1-yl]pyrimidin-4-amine, N-(Cyclopropylmethyl)-6-[3-(methylamlno)pyrrolidln-1-yl]pyrimidin-4-amine, N-(3,3-Dimethylbutyl)-6-[3-(methylamino)pyrrolidin-1-yl]pyrimidin-4-amine, 6[3-(Dimethylamino)pyrrolidin-1-yl]-N-(3,3-dimethylbutyl)pyrimidin-4-amine, N-(Cyclopropylmethyl)-6-[3-(dimethylamino)pyrrolidin-1-yl]pyrimidin-4-amine, 6-[3-(Dimethylamino)pyrrolidin-1-yl]-N-sobutylpyrimidin-4-amine, 6-[3-(Dimethylamtno)pyrrolidin-1-yll-N-ethylpyrimidin-4-amine, 6-[3-(Dimethylamino)pyrrolidin-1-yl]-N-(2,2-dimethylpropyl)pyrimidin-4-amine, N-(3,3-Dimethylbutyl)-6-[octahydro-6H-pyrrolo[3,4-b]pyridin-6-yi]pyrimfdin6-2,4-diaminie, N4-[sopropyl-6-[octahydro-6H-pyrrolor3,4-b]pyridin-6-yl]pyrimidin6-2,4-diamme, N4-Methyl-6-[octahydro-6H-pyrrolo{3,4-b]pyridin-6-yl]pyrimidin6-2,4-dfamine, N4-Ethy]-6-[octahydro-6H-pyrroloI3,4-b]pyridin-6-yl]pyrimidin6-2,4-diamine, N4-Isobutyl-6-Ioctahydro-6H-pyrroloI[3,4-bJpyridin-6-yl]pyrimidin6-2,4-dJamine, N4-(Cyclopropylmethyl)-6-toctahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]pyrimidinie2,4-diamine, N4-(3-Methylbutyl)-6-[octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]pyrimidin6-2,4-dtamine, N4-(2,2-DimethylpropyI)-6-[oc1ahydro-6H-pyrrolo[3,4-b]pyridir3-7-yl]pyrimidin6-2,4-diamirie, N4-Cyclopropyl-6-[ootahydro-6H-pyrrolop,4-blpyridin-6-yl]pyrimidin6-2,4-diamine, N4-Cydobutyl-6-[octahydro-6H-pyrroloI3,4-b]pyridin-6-yli]pyrimidin6-2,4-diamine, N4,-(Cyclopenty]methyl)-64ocrtahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]pyrimidin6-214-diamine, 6-[5-Methylhexahyclropyrrolo[3,4-c]pyrrol-2{1H)-yl]-N-propylpyrimidin6-2,4-diamine, N4-Methyl-6-[5-melhylhexahydrdpyrroto[3,4-c]pyrrol-2{1H)-yl]pyrimtdin6-2,4-dJaiTiinie, N4-Ethyl-6-[5-methylhexahydropyrrolol[3,4-clpyrrol-2(1H)-yl]pyrimidine2,4-diamine, N4-lsobutyl-6-[5-methylhexahydropyrroIo[3,4-clpyrro]-2(1H)-yl]pyrimidin6-2,4-diamine, N4-(Cyclopropylmettiyl)-6-[5-methylhexahydrapyrrdo[3,4c]pyrro]-2(1H)-yl]pyrimidin6-2,4-diamirie, N4-(2,2-Dirnethylpropy!)-6-[5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]pyrimrdin6-2,4-diamine, N4-(3,3-DimethylbutyI)-6-[5-methylhexahydropyrraIo[3,4-c]pyrrol-2(1H)-y]]pyrimidin6-2,4-diamine, N4-(3-Methylbutyl)-(H5-methylhexahydropynolo[3,4-c]pyrrol-2(1H)-yl]pyrim!din6-2,4-diamine, N4-Cyc!opropyl-6-[5-methylhexahydropyvrolo[3,4-c]pyrrol-2(1H)-yl]pyrimidin6-2,4-diamtrie, N4-Cyclobutyl-6-[5-methylhexahydropyrrolo[3,4-c]clpyrrol-2(1H)-yl]pyrimidin6-2,4-diamine, Cyclopropylmethyl-[6-(3-metbylamino-azetidin-1-yl)-pyrimldin-4-yl]-amine, {3-Fluoro-benzyl)-[6-(3-methylamino-a2etidln-1-yl)-pyrimidin-4-yl]-amine, N-lsopropyl-6-[3-(methylamino)azetidin-1-yl]pyrimidin-4-amine, N-(4-Fluorobenzyl)-6-I3-(methylamino)azetidln-1-yl]pyrimidin-4-amine, N-Ethyl-6-[3-(methylamino)azetidm-1-yl]pyrimidin-4-amine, N-lsobutyl-6-[3-(mejthylamino)azetidin-1-yl]pyrimidin-4-amine, 2-({6-[3-(Methylamino)azetidin-1-yl]pyrimidin-4-yl}arnino)sthanal, N-BenzyI-6-[3-(methy]amino)azetidin-1-yl]pyrJmidin-4-amine, N-(2-Chlorobenzyl)-6-[3-(methylamino)azetidin-1-yl]pyrimidin-4-amine, N-MethyH-[6-(4-methylpiperldin-1-yl)pyrimidln-4-yl]azetidln-3-am!ne, N-(2-Methoxyethyl)-6-[3-(methylamino)azetidin-1-yl]pyrimidin-4-amine, 6-[3-(Methy]amino)azetidin-1-yl]-N-(3-methy)butyl)pyrimidin-4-aniine, N-Methyl-1-(6-piperidin-1-ylpyrimidin-4-yl)a2etidin-3-amine, N-(2,2-Dimethylpropyl)-6-[3-(methy]amino)azetidin-1-yl]pyrimidin-4-amlne, N-Methyl-6-[3-(me1:hylamino)azetidin-1-yl]pyrimidin-4-amine, N-(3,3-Dimethylbutyl)-6-[3-(methylamino)azetidin-1-yl]pyrimidfn-4-amine, N-lsopropyl-6-(3-methylamino-azetidin-1-yl]-pyrimidin6-2,4-diamine, N,-(2,2-Dimethylpropyl)-6-[3-{methylamino)azetidin-1-yl]pyrimidin6-2,4-diamine, 6-(3-Methylamino-;azetidin-1-yl)-N4-(3,3,3-trifIuoro-propyl)-pyrimidin6-2,4-diamine, N4-Cyclopropylmethyl-6-(3-methylaminoazetidin-1-yl]-pyrimidin6-2,-diamine, N4-{3,3-Dimethyl-butyJ)-6-{3-methylarnino-aze{idiin-1-yl)-pyrimidin6-2,4-dianfiiJne, N4-{3-Fluoro-benzyl)-6-(3-methylamino-azetidin-1-yl}-pyriniid[n6-2,4-diamirie, N4-{3-Methoxy-benzyl)-6-(3-methylamino-azetidln-1-yl)-pyrimidin6-2,4-diamire, N4-Cyclobutylmethyl-6-f3-methylamino-azetidin-1-yl]-pyrimtdin2,4-diamline, N4-Cydopentylmethiyl-6-[3-methylamino-azetidin-1-yll-pynrnidjn6-2,4-minie, N4-Methyl-6-[3-(fnethylamino)azetidin-1-yl]pyrimidin6-2,4-dtamiiie, N4-Ethyl-6-[3-(methylamino)azetidin-1-yl]pyrimidin6-2,4-diamine, N4-Ssobutyl-6-[3-(melhylamino)azeldin-1-yl]pyrimidin6-2,4-diamine, N4-Cyclopropyl-6-I3-(methylamino)azetid)iri-1-yi]pyrimidiri6-2,4-diaininier 6-[3-(Methy!amino)iazetidin-1-yl]-N4-propylpyrimidiri6-2,4-dlamine, 6-[3-(Methylamino);3zefidin-1-yl]-N4-(3-methylbulyl)pyrimidin6-2,4-diamine, N-Cydobutyl-6-[3-itmethylaminoJazetidin-1-yl]pyrimidine2,4-diamiiie, 6-[3-(Methylamino)azetidin-1-yl3-2,44-(trifluoromethoxy)berizyl]pyrimidin6-2,4-diamirie, 4-[({2-Amino-6-[3-(methylamino)azetidiri-1-yl3pyriin1diri-4-y(}amino)rnethyl]benzonitrile, N4-(2-Fluorobenzyl)-6-[3-(metiiylamino)a2etidin-1-yl]pyrimidiii6-2,4-dfamine, N4-Benzyl-6-[3-(methylamino)azetidin-1-yl]pyrimidin6-2,4-diamine, 6-3-(MethylarninoJazetidin-1-yll-N-[3-(trifluoromethyl]benzyl]pyrimidin6-2,4-diarriine, N4-{4-Chlorobenzyl)-6-[3-(methylamino)azetidin-1-yl]pyrimidin6-2,4-diamine, 6-{3-(Methylamino)azetidin-1-yl]-N4-(2-methylbenzyl)pyrimidin6-2,4-diamirie, 6-[3-(Methylamino)azetidin-1-y\]-N4-(3-melhylbenzyl)pyrimidin6-2,4-diamine, 6-[3-(Methylamino)azetidin-1-yl3-N4-[2-(trifiuoromethy1)benzy]pyrimidin6-2,4-diarninel 6-[3-(Wlethylamino)azetidin-1-yl]-N4-[4-(trifluoromethyl)benzyl]pyrimldin6-2,4-diamine, N4-(3-ChIorobenzyl)-6-[3-(methylamino)azetidin-1-yl]pyrlmidin6-2,4-diamine, N4-{2-Methoxybemyl)-6-[3-(melhylamino)azetidin-1-yl]pyrimidin6-2,4-diarnirie, B-[3-(Methylamino)azetidin-1-yl]-N4-(4-methylbenzyl)pyriniidin6-2,4-diamine, N4-(2-Chlorobenzy])-6-[3-(methylamino)azetidin-1-yl]pyrinnldin6-2,4-diamine, N4-(4-Fluorobenzyl)-6-[3-(methylamino)azetidin-1-yl]pyrimidin6-2,4-diamine, N4-(3-F]uorobenzyl)-6-(4-methylpiperazin-1-yl)pyrImidin6-2,4-diaminel N4-(3-Fluorobenzyl]-6-[5-methylhexahydropyrrolo[3,4c]pyrrol-2(1H)-yl]pyrimidine2,4-diarnine, N4-(3,3-Dimethylbutyl)-6-[3-methylpiperazin-1-yl]pyrimidine2,4-diamine, N4-(2,2-DimethylpropyI)-6-[3-methylpiperazin-1-yl]pyrimidin6-2,4-diamine, N4-Ethyl-6-[3-metbylpiperazin-1-yl]pyrimidin6-2,4-diamine, N-(2,2-Dimethylpropyl)-6-(4-metliylpiperazin-1-yl}pyrimidin-4-aminel N-(3-MethylbutyI)-6-(4-methy]piperazin--t-yl)pyrimidin-4-amine, N4-(3,3-Dimethylbutyl)-NB-tpyrrolidin-3-yl]pyrimidin6-2,4,6-triamine, N4-(3,3-Dimethylbutyl)-6-(4-methylpiperazin-1-yl)pyrimfdin6-2,4-dlamine, N-Ethyl-6-(4-methylpiperazin-1 -yl)pyrimidin-4-amine, N-lsopropyl-6-(4-methylpiperazin-1-yl)pyrimiidin-4-amirie, N-lsobutyl-6-(4-methylpiperazin-1-yl)pyrimidin-4-amine, N-(Cyclopropy!methyl)-6-(4-methylpiperazin-1-yl)pyrimidin-4-amine, N-(3-MethyJbutyl)-N-[pyrrolidin-3-yl]pyrimidin6-4,6-diaminer N4-(3-Methylbutyl)-6-(4-metliylpiperazin-1-yl)pyrimidin6-2,4-diaminel N-(2-Methoxyethyl)-6-(4-methylpiperazfn-1-yl)pyrimidin-4-amine, N-(3,3-Dimethylbutyl)-6-pipera2in-1-ylpyrimidin-4-amine, 6-(4-Methylpiperazin-1-yt)-N-[tetrahydrofuran-2-ylmethyl]pyrimidin-4-amine, 4-(4-Methylpiperazin-1 -yl)-6-pyrroIidin-1 -ylpyrimidine, 6-(4-Methylpiperazin-1-yl)-N-(3,3,3-trifluoropropy])pyrimidin-4-aminie, N-isobutyl-5-methyl-6-(4-methylpiperazin-1-y[)pyrimidin-4-amine, N-Ethyl-6-[5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1.H)-yl]pyrimidin-4-amline, 6-(3-Aminoazetidin-1-yl)-N-[3,3-dimethylbutyl)pyrimidin-4-amine, N4-)sopropyl-6-(4-methylpiperazin-1-yl)pyiimidin6-2,4-diamine, N-Ethyl-6-methylpiperazin-1-yl)pyrimidine2,4-dlamine, N-lsobutyl-6-methylpiperazin-1-yl]pyiimidine2,4-diamine, N4-(Cyclopropylmethy])-6-(4-metliylpiperazin-1-yl)pyrimrdin6-2,4-diatnine, N-(Cyclopropylmethyl)-6-[octahydro-6H-pyrrolo[3,4-b]pyridiri-6-yiIpyrirnidin-4-arnirie, N4-(3,3-Dimethylbutyl)-6-[3,4-dimethy[piperazin-1-yl]pyrimidin6-2,4-diarnine, N-lsobutyl-6-Ioctahydro-[3pyrrolo[3,4-b]pyridin-6-yl]pyrimidin-4-amine, 6-[ 6-Amino-3-azatiicyclo[3.1.0]hex-3-yl]-N4-(2,2-dimethy]propy!)pyrimidin6-2,4-diamine, N-(2,2-Dimathylpropyl)-6-[octahydro-6H-pyrrolo[3,4-b]pyiidin-6-yl]pyrimidiri-4-amine, 6-[3-(Methylamino)azetidiri-1-yl]-N4-(2-methylbutyl)pyiimldin6-2,4-diamirie, N4-[(1 S)-1,2-Dimethylpropyl]-6-[3-(methy(amino)azetidin-1 -yl]pyrimidin6-2,4-diamine, N4-(2,5-Difluorobenzyl>-6-I3-{methylamino)azetidin-1-yl]pyrimidin6-2,4-diamine, N4-(2,3-Difluorobenzy))-6-[3-(mefriy]amino)azettdin-1-yl]pyrimldin6-2,4-diaminel N4-Butyl-6-[3-(methylamino)azetidin-t-yl3pyrimidin6-2,4-diannine1 6-(1,4-Diazepan-1-yl)-N4-isobutylpyrimidin6-2,4-diamine, 6-[(3R)-3-(Methylaimino)pyrrolidin-1-yl]-N4-(2-methylcyclopropyl)pyr[midin6-2,4-dramine, N4-lsobuty]-6-(4-methyl-1,4-diazepan-1 -yI)pyrimidin6-2,4-diamine, N4-{CycIopropylmethyl)-6-(3-pyrrolidin-1-ylazetidin-1-y])pyrimidin6-2,4-diamine, N4-lsopropyl-6-E(3aR*,7aS*)-octahydro-5H-pyrrolo[3,2-c]pyrid[n-5-yl]pyrimfdin6-2,4-diamine, N4-Bicyclo[1.1.1]pent-1-yl-6-[(3R)-3-(methylamino)pyrrolidin-1-yl]pyrimidin6-2,4-diamine, 6-(4-Aminopiperidin-1-yl)-N4-ethylpyrimidin6-2,4-diamine, 6-[3-Methyl-3-(me1:hylamino)azetidin-1-yl]-N4-propylpyrinnidin6-2,4-diamme, N4-(2,2-D'')methylpropyl)-6-(hexahydropyrrolo[1,2-a]pyrazlrt-2(1H)-yl)pyrimidin6-2,4-diamine, N4-(2,2-Dimetliylpiropyl)-6-(3-pyn''olidin-1-ylazetidin-l-yl)pyrimidin6-2,4-diamine, N4-(2,2-Dimethylpiropyl)-N6-[2-(methylamJno)efriyl]pyrimldin6-2,4,B-triamlne, N4-[2-(Dimethylamino)ethyl]-NB-(2,2-dimethylpropyl)pyrimidin6-2,4,6-triamine, N4-(2,2-Dimethylpropyl)-6-[3-CisopropyIamino)azetidin-1-yl]pyrimidin6-2,4-diamine, E)-[(3R)-3-(Methylamino)pyrrolidin-1-yl]-N-[(1R)-1-methylpropyl]pyrimidin-4-amine, N-Buty!-6-[(3R)-3-(methylamino)pyrrolidin-1-yl]pyrimidin-4-amine, N4-(tert-Butyl)-6-[(3R)-3-(methylamino)pyrrolidin-1-yl]pyrimidin6-2,4-diamiri6, 6-[{3R)-3-1-Benzvlpyrrolidin-3-vn-fV-(3,3-dimethvlbutv^pvTimidin6-4,6-diaTnine The title compound Nas prepared by a method similar to that described for preparation 20, using the title compound of preparation 8, in 48% yield. MS (APCI) m/z 354 [M+H]+ Preparation 22: teit-Sutvl fl -r6-tcvcloproPv[methvl-aminoVDvrimidin-4-vfl-azetidliri-3-vl>-iTiethvl-carbamate To a 5 mL reacti-vial™ containing the title compound of preparation 1 (100 mg, 0.33 mmol) and cyclopropylrnethylamine {50 mg, 0.68 mmol) in DMSO (3 mL) Nas added TEA {94 µL, 0.68 mmol) and the solution Nas heated at 140 °C for 18 hours. The reaction Nas alloNed to cooi to ambient temperature, loaded onto a 5g SCX column, eluted Nith MeOH (100 mL) folloNed by 2M ammonia in MeOH (100 mL). Fractions containing product (as judged by TLC) Nere combined and evaporate to give a crude orange oil. The crude product Nas purified by flash column chromatography on silica gel eluting Nith DCM : MeOH (99 :1 changing to 96:4 by volume) to yield the title compound as a colourless oil (75 mg, 67%). 1H NMR (400MH:z, CDCI3): 5 8.13 (1H, s), 5.08 (1H, s), 4.79 (1H, br s), 4.20 (2H, t), 4.01 (2H, m), 3.04 (2H, t), 2.93 (3H, s), 1.46 (9H, s), 1.05 (1H, m), 0.55 {2H, m), 0.24 {2H, m) ppm. MS (APCI) m/z 334 [M+H]+ Preparation 23: tret-Butvl {1-[6-(3-fluoro-benzvlamino)-pynmidin-4-yn-azettdin-3-vl)-methvl-carbamate (Formula Removed) To a 5ml reacti-vial™ containing the title compound of preparation 1 (100 mg, 0.33 mmol) and 3-fluorobenzylamlne (76 µL, 0.68 mmol) in DMSO (3 mL) Nas added TEA (9 µL, 0.6B mmol) and the solution Nas heated at 140 °C for 18 hours. The reaction Nas alloNed to cool to ambient temperature and concentrated in vacuo to obtain crude product as a viscous orange oil. The crude product Nas purified by flash column chromatography on silica gel eluting Nith DCM;: MeOH (99:1 changing to 97 : 3 by volume) to yield the title compound as a light beige coloured solid (49 mg, 38%). 1H NMR {400MHz, CDCt3): 6 8.18 flH, s), 7.30 {1H, m), 7.09 (1H, rn), 7.02 (1H, d), B.97 (1H, m), 5.09 (1H, s), 5.0 (1H, brd), 4.46 (2H, d), 4.17 (2H, t), 3.98 (2H, m), 2.92 (3H, s), 1.47 (9H, s) ppm. MS (APC1) m/z 388 [M+H]+ Preparation 24: tert-Butvl (4aR*.7aR*)-6-(2-amino-6-[(3,3-dimethvlbutvl)anlno]pyrimidin-4-vl)octahvdro-1H-pvrrolor3.4-blpvrldln6-1-carboxvlate To a solution of the title compound of preparation 14 (80 mg, 0.17 mmol) in DMSO (150 µL) Nas added 3,3-dimethylbutan-1-amine (229 µL, 1.7 mmol) and the reaction mixture Nas heated to 120 °C in a sealed vessel for 48 hours. The reaction mixture Nas diluted Nith Nater (4 mL) and extracted Nith ethyl acetate (4 mL). The organic extract Nas dried (MgSO4) and concentrated in vacuo. The residue Nas dissolved in MeOH (0.5 ml) and purified using a phenomomnex HPLC C-18 column eluting Nith acetonjtrile:Nater {5 : 95 changing to 95 : 5 by volume containing 0.1% TFA by volume) to yield the title compound as a gum (45 mg, 63%). 1H NMR (400MHz, CDCl3): 5 8.41 - 8.33 (1H, m), 7.6 - 7.3 (1H, m), 6.15 (1H, br s), 4.92 - 4.69 (1H, rn), 4.65 (1H, s), 4.05 (1H, d), 3.89 - 3.19 <5H, m), 3.17 - 3.09 (2H, rn), 2.77 (1H, t), 2.39 - 2.19 (1H, m), 1.88 -1-65 (2H, m), 1-62-1.51 (2H, m), 1.49 (9H, s), 1.44-1.17 (1H, m) 0.97 (9H, s) ppm. MS (ESI) m/z 419 [M+H]* Preparation 25: tert-Butvl (1-f2-amino-6-^2,2-dimethvlproovl!iaminoTpvrimidin-4-vllazetidin-3-vUmethvl-carbamate (Formula Removed) To a solution of the title compound of preparation 12 (40 mg, 0.13 mmol) in DMSO (150 µL) Nas added isopropylamine (150 µL, 1.7 mmol) and the resulting mixture Nas heated to 120 DC in a sealed vessel for 48 hours. The reaction mixture Nas concentrated in vacuo to give a broNn gum. The residual gum Nas purified by flash column chromatography on silica gel eluting Nith DCM : MeOH : 0.880 ammonia (990 : 10:1 changing to 190:10 :1 by volume) to yield the title compound as a gum (20 mg, 42%). ''H NMR (400MHz, CD3OD): 5 4.83 (1H, s), 4.13 (2H, t), 3.97 (2H, dd), 3.01 (2H, s), 2.93 (3H, s), 1.46 (9H, s), 0.94 (9H, s) ppm. MS (ESI) m/z 365 [M+H]+ Preparation 26: tret-Butvl [1-[2-amino-6-isopropvlamino-pyrimidin-4-vl]-azetldin-3-yl]-methyl-carbamate (Formula Removed) To a solution of the title compound of preparation 12 (40 mg, 0.13 mmol) in DMSO (150 µL) Nas added isopropylamine (150 µL, 1.7 mmol) and the resulting mixture Nas heated to 120 QC in a sealed vessel for 48 hours. The reaction mixture Nas concentrated in vacuo to give a broNn gum. The residual gum Nas purified by flash column chromatography on silica gel eluting Nith DCM : MeOH : 0.880 ammonia (990 : 10:1 changing to 190:10 :1 by volume) to yield the title compound as a gum (22 mg, 50%). 1H NMR (400MHz, CDCl3): 5 4.95 (1H, br s), 4.67 (1H, s), 4.4S (2H, br s), 4.33 (1H, br d), 4.16 (2H, brt), 3.95 (2H, dd), 3.72 (1H, m), 2.92 (3H, s), 1.46 (9H, s) 1.19 (6H, rj) pprn. MS (APCI) m/z 337 [M+H]+ Preparation 27: fert-Butvl H-r2-amino-6-f3.3,3-trifluorQH3ropvlamino''>-Dvrimidin-4-vll-azetidm-3-vlV-methvl-carbamate (Formula Removed) To a solution of the title compound of preparation 12 (30 mg, 0.1 mmol) in EtOH (200 pL) Nas added 3,3,3 trifluoropropylamine hydrochloride (48 mg, 0.3 mmol) folloNed by TEA (100 µL, 0.7 mmol) and the resulting mixture Nas heated under microNave irradiation to 130 °C in a sealed vessel for 90 min. The reaction mixture Nas concentrated in vacuo to give a broNn gum. The residual gum Nas purified by flash column chromatography eluting Nith DCM : MeOH : 880 ammonia (99 : 1 :0.1 changing to 95 : 5 : 0.5, by volume) to yield the title compound as a gum (15 mg, 38%). 1H NMR (400MHz, CD3COCD3): 8 5.71 (1H, brt), 5.13 (2H, br s), 4.87 (1H, br s), 4.84 (1H, s), 4.04 (2H, t), 3.88 (2H, dd), 3.54 (2H, q), 2.91 (3H, s), 2.52 (2H, m), 1.44 (9H, s) pprn. MS (APCI) mfe 391 [M+H]+ Preparation 28: tert-Butvl (1 -[2-amino-6-(cvciopropvlmethvl-aminQ^-pyrimidin-4-vn-azetldin-3-vlV-methvl-carbamate The title compound Nas prepared by a method similar to that described for preparation 26, using the title compound of preparation 12 and cyclopropylmethylamine, In 48% yield. 1H NMR (400MHz, CD3COCD3): 5 5.51 <1H, m), 5.03 (2H, br s), 4.87 (1H, br s), 4,79 (1H, s), 4.03 (2H, t), 3.87 (2H, dd), 3.08 (2H, t), 2.90 (3H, s), 1.43 (9H, s), 1.02 (1H, m), 0.42 (2H, m), 0.19 (2H., m) ppm. MS (APCI) m/z 349 [M+H]+ Preparation 29: tert-Butvl f 1 -T2-amino-6-f3.3-dimethv)-tautSflamtnioVDvrimid1n-4-vn-azetidln-3-vn-methvl-carbamate The title compound Nas prepared by a method similar to that described for preparation 26, using the title compound of preparation 12 and 3,3-dimethylbutan-1-amine, in 58% yield. 1H NMR (400MHz, CDC13): 5 5.0 (1H, br s), 4.67 (1H, s}, 4.52 (2H, br s), 4.36 (1H brt), 4.16 (2H, t), 3.86 (2H, m), 3.13 (2H, m), 2.32 (3H, s), 1.50 -1.45 (11H, m), 0.95 (9H, s) ppm. MS (APCI) m/z 379 [M+H]+ Preparation 30: tert-Butvl {1-r2-amino-6-(3-fluoro-benzylamino)-pvrimidin-4-vl)-azetidin-3-yl)- methyl-carbamate (Formula Removed) The title compound Nas prepared by a method similar to that described for preparation 26, using the title compound of preparation 12 and 3-fluorobenzylamine using 1,2-diethoxy-ethane as reaction solvent, in 53% yield. 1H NMR (400MHz, CDCI3): 5 7.28 (1H, m), 7.08 (1H, d), 7.01 (1H, brd), 6.95 (1H, br t), 5.15 (1H, brt), 5.00 (1H, brs), 4.30 (2H, brs), 4.64 (1H, s), 4.41 (2H, br d), 4.13 (2H, t), 3.96 (2H, dd), 2.90 (3H, s), 1.45 (9H, s) ppm. MS (ESI) m/z 403 [M+H]+ Preparation 31: tert-Butvl ^1-r2-amino-6-f3-methoxv-benzvlamino)-Dvrimidin-4-vll-azetidin-3-vlV methvl-carbamate (Formula Removed) The title compound Nas prepared by a method similar to that described for preparation 26, using the title compound of preparation 12 and 3-methoxy-benzylamine, in 17% yield. 1H NMR (400MHz, CD3COCD3): B 7.20 (1H, t), 6.93 - 6.89 (2H, m), 6.78 {1H, dd), 5.96 (1H, br t), 5.12 (2H, br s), 5.00-4.70 (2H, m), 4.46 (2H, d), 4.01 (2H, t}, 3.86 (2H, m), 3.76 (3H, s), 2.90 (3H, s), 144 (9H, s) ppm. Preparation 32: tret-Butvl {1-12-amino-6-(cyclobutvlmethyl-amino)-pvrimidin-4-vl]-azetidin-3-vl]-methvl-carbamate To a solution of the title compound of preparation 1 (30 mg, 0.10 mmol) in DMSO (15D µL) Nas added cyclobutylmethylamlne hydrogen chloride (127 mig, 1 mmol) folloNed by DIPEA ( 300 µL, 1.76 mmol) and the resulting mixture Nas heated to 120 °C in a sealed vessel for 48 hours. The reaction mixture Nas concentrated in vacuo to give a gum. The residual gum Nas purified by flash column chromatography on silica gel eluting Nith DCM : MeOH : 0.880 ammonia (990 : 10 :1 changing to 190 : 10 : 1 by volume} to yield the title compound as a gum (12 mg, 33%). 1H NMR (400MH:z, CD3COCD3): 5 5.52 (1H, m), 5.13 {2H, br s), 4.87 (1H, br s), 4.79 {1H, s), 4.05 (2H, t), 3.86 (2H, dd), 3.25 (2H, t), 2.91 (3H, s), 2.56 (1H, m), 2.05 -1.97 (H, m), 1.89 -1.80 (2H, m), 1.77 -1-69 (2H, m), 1.44 (9H, s) ppm. MS (ESI) m/z 363 [M+H]+ Preparation 33: tert-Butvl {1-12-amino-6-(cvcloDentvlmethvl-amino)Pvrimidtn-4-vn-a2etid[n-3-yl}-methvl-carbamate (Formula Removed) The title compound was prepared by a method similar to that described for preparation 26, using the title compound of preparation 12 and cycloperrtylmethylamine hydrogen chloride, in 16% yieid. 1H NMR (400MHz,''CD3OD): 8 4.79 (1H, s), 4.15 (2H, t),4.00 (2H, dd), 3.10 {2H, d), 2.93 (3H, s), 2.14 (1H, m), 1.83 -1.75 (2H, m), 1.69 -1.53 (4H, m), 1.46 (9H, s), 1.3Q -1.22 (2H, m) ppm. MS (APCI) m/z 377 [M+H]+ Preparations 34 to 42 The folloNing compounds of the general formula shoNn beloN Nere prepared by a metiiod similar to that described for preparation 1 using the appropriate amine and 2-amino-4,6-dichloropyrimidine. Reactions Nere monitored by TLC analysis. (Formula & Table Removed) Preparation 43: N4-(tert-Butyl)-6-chl6ropvrimidin6-2.4-diamine A solution of 2-amlna-4,6-drchloropyrimidine (400mg, 2.44mmol) and t-butylamine (2.6ml, 25.0mmol) in NMP (1ml) Nas heated in a microNave at 150°C for 60 minutes. The reaction mixture Nas partitioned betNeen Nater (10ml) and ethyl acetate (10ml), the organic phase separated, dried and reduced in vacuo. Purification by flash column chromatography on silica gei eluting Nith ethyl acetate:pentane (30:70 changing to 80:20 by volume) to yield the title compound as a colourless solid (494mg, 100%). 1H NMR (400MHz, CDCI3): 6 5.80 (1H, s), 4.78 (2H, bs), 1.42 (9H, s) ppm. MS (ESI) m/z 201 [M+H]+ Preparation 44:6-Chloro-N4-(1 -methvlcvclopropvl)PVrimidin6-2,4-d lamlne 2-amino-4,6-dichJoropyrimidine (508mg, 3.1mmot) Nas added to a suspension of 1-methylcyclopropylamine hydrochloride (1.0g, 9.3mmol) and sodium methoxtde (502mg, 9.30mmol) in NMP (3ml). The resulting mixture Nas heated at 90°C for 16 hours and then cooled to room temperature. The reaction mixture Nas diluted Nith Nater (20ml) and the resulting precipitate filtered off, Nashed Nith further Nater (20ml) and dried in vacuo to give the title compound as a colourless solid (280rng, 15%). 1H NMR (400MHz, CDCI3): 5 6.71 (1H, s), 1.37 (3H, s)r 0.83-0.79 (2H, m), 0.72-0.65 (2H, m) ppm. MS (ESI) m/z 199 [M+H]+ Preparation 45 : Benzyl (3R)-3-f(fert-butoxvcarbonvnaiTimolPvrrolidin6-1-carboxvlate A solution of te/f-Butyl (3S)-pyrrolidin-3-ylcarbamate (10.0g, 53.7mmol) in DCM (40ml) Nas treated Nith TEA (14.9ml, 107mmol) and cooled to 0°C. Benzyl chloroformate (7.6ml, 53.7mmol) Nas added dropNise and the resulting suspension Nas alloNed to Narm gradually to room temperature over a period of 18 hours. The reaction mixture Nas diluted Nith Nater (100ml) and the organic phase separated. The aqueous phase Nas extracted Nith further DCM (2 x 50ml) and the combined organic extracts dried (sodium sulphate) and concentrated in vacuo to give a pale yelloN solid (14.6g, 85%) ''H NMR (400MHz, CDCI3): 3 7.39-7.29 (5H, m), 5.13 (2H, s), 4.58 (1H, m), 4.19 (1H, m), 3.66 (1H, m), 3.49 (1H, m), 3.25 (1H, m), 2.14 (1H, m), 1.82 (1H, m), 1.44 (9H, s) ppm. MS (ESI) m/z 321 [M+H]+ Preparation 46 : Benzyl <3R)-3-ntert-butoxvcarbonvnaminolPvrrolidin6-1-carboxvlate (Formula Removed) A solution of the carbamate of preparation 45 (14.6g, 45.6mmol) in THF (85ml) Nas cooled to 0°C and treated Nith potassium tret-butoxide (4.38g, 59.27mmol). The reaction Nas left to stir for 30 minutes prior to the addition of methyl iodide (4.26ml, 59.3mmol) and then allowed to Narm gradually to room temperature. The reaction mixture Nas partitioned betNeen ethyl acetate (200ml) and Nater (1 DOml). The aqueous phase Nas separated and extracted Nith further ethyl acetate (100ml). The combined organic extracts Nere Nashed Nith saturated aqueous sodium chloride (100ml), dried (magnesium sulphate) and reduced in vacuo to give an orange oil. The oil Nas r6-dissolved in THF (85ml), cooled to 0°C and treated Nith potassium tret-butoxide (3.00g, 40.6mmol). The reaction Nas left to stirfor 30 minutes prior to the addition of methyl iodide (3.0ml, 41.7mmol) and then alloNed to Narm gradually to room temperature. The reaction mixture Nas partitioned betNeen ethyl acetate (2Q0ml) and Nater (100ml). The aqueous phase Nas separated and extracted Nith further ethyl acetate (100ml). The combined organic extracts Nere Nashed Nith saturated aqueous sodium chloride (100ml), dried (magnesium sulphate) and reduced in vacuo to give the title compound as an orange oil (15.3g, 100%). 1H NMR (400MHz, CDCI3): 6 7.35-7.26 (5H, m), 5.11 (2H, s), 4.70 (1H, m), 3.58 (2H, m), 3.34 (1H, m), 3.29 (1H, m), 2.74 (3H, s), 1.99 (2H, m), 1.43 (9H, s) ppm. MS (ESI) m/z 335 [M+H]+ Preparation 47 : fert-Butvl methvir(3R)-DvrroNditi-3-vncarbamate A solution of the carbamate of preparation 46 {15.5Bg, 46.6mmoi) in ethanol {150ml) Nas hydrogenated in the presence of 5%Pd/C (1g) at 50psi at room temperature for a period of 18 hours. Further PdVC (500mg) Nas added and the resulting mixture hydrogenated under the same conditions for a further 26 hours. The catalyst Nas filtered off and the filtrate concentrated In vacuo. Purification by chromatography (DCM:MeOH:0.880 ammonia (100:0:0 changing to 90:10:1 by voiurne) gave the title compounds as a pale yelloN oil (5.85g, 62%). 1H NMR (400MHz, CDC!3): 8 4.56 (1H, m), 3.06 (2H, m), 2.87 (1H, m), 2J9 (1H, m), 2.78 (3H, s), 2.54 (1H, s), 1.95 (1H, m), 1.73 (1H, m), 1.43 (9H, s) ppm. MS (ESI) m/z 201 P+H]+ Example 1: N-(3.3-Dimethvlbutvn-6-(4-methviplperazin-1-vftpvrlmidin-4-amine A solution of the title compound (110 mg, 0.52 mmal) of preparation 6 In NMP (2 mL) Nas treated Nith DIPEA (135 µL, 0.78 mmol) and 3,3-dimethylbutan-1 -amine (347 pi, 2.6 mmal) and heated to 150 °C for 18 hours in a sealed vessel. The reaction mixture Nas cooled to ambient temperature and partitioned betNeen ethyl acetate (20 mL) and Nater (20 mL). The organic fraction Nas Nashed Nith saturated aqueous sodium chloride (20 mL) dried (MgSO4) and concentrated in vacuo. The residue Nas purified by flash column chromatography on silica get eluting Nith DCM : MeOH : 0.880 ammonia (90 : 10 : 1 by volume) to yield the title compound as a gum (57mg, 40%). 1H NMR (400MHz, CD3OD): 5 7.95 <1H, s), 5.56 (1H, s), 3.51 (4H, m), 3.23 (2H, m), 2.47 (4H, m), 2.30 (3H, s), 1.49 (2H, m), 0.95 (9H, s) ppm. MS (APCI) m/z 278 [M+H]+ Examples 2 to 5 The folloNing compounds Nere prepared by a method similar to that described for example 1 using the appropriate starting material. (Table Removed) Example 6: N-(3.3-Dimethvlbutvl)-N-[(3S)-pvrrolidin-3-vnpvrimidin6-4,6-diamine (Formula Removed) A solution of the compound of preparation 20 (2.15 g, 6.1 mmol) in EtOH (40 mL) and MeOH (20 mL) Nas cooled to 0 °C and treated Nith palladium hydroxide (20% on carbon 100 mg) folloNed by ammonium formate (5.8 g, 91 mmol) and heated to reflux for 2 hours. The reaction mixture Nas cooled to ambient temperature filtered and the filtrate concentrated in vacuo. The residue Nas purified directly by SCX resin, eluting non-basic compounds Nith MeOH and the basic compounds Nith 1N ammonia in MeOH. The basic Nashings Nere concentrated in vacuo and purified by flash column chromatography on silica gel eluting Nith DCM : MeOH : 0.880 ammonia (1:0:0 changing to 80 : 20 : 1, by volume) to yield the title compound as a Nhite poNdery solid (1.2 g, 75%). 1H NMR (400MHz, CD3OD): 5 7.9 (1H, s), 5.4 (1H, s), 4.1 (1H:, m), 3.2 (2H m), 3.1 (1H, m), 3.0 (1H, m), 2.9 (1H, m), 2.7 (1H, m), 2.1 (1H, m), 1.7 (1H, m), 1.5 (2H, m}, 1.0 {9H, s) ppm. Accurate mass: found 264.2181, C14H26N5 requires 264.2-f 83. Example?: N-{3.3-Dimethylbutyl)-N''-[(3R)-pyrrolidin-3-ynpyrimidin6-4.6-diamine (Formula Removed) The title compound Nas prepared by a similar method to that described for example 6, using the title compound of preparation 21, in 70% yield. H NMR (400MHz, CD3OD): 5 7.9 (1H, s), 5.4 (1H, s), 4.1 (1H, m), 3.2 (2H m), 3.1 (1H, m), 3.0 (1H, m), 2.9 (1H, m), 2.7 (1H, m), 2.1 (1H, m), 1.7 (1H, m), 1.5 (2H, m), 1.0 (9Hr s) ppm. MS (APCI) m/z 264 [M+H]+ Example 8: ^-f3.3-Dimethylbutyl)-ftr-rf3ffl-1-methvipvrrolidiri-3-vllpyrim3dln6-4,6-diatnirte (Formula Removed) A suspension of the compound of example 7 (38 mg, 0.144 mmol) in THF (1.5 mL) containing aqueous formaldehyde (11 µL, 0.144 mmol, 37% in Nater) and acetic acid (8.3 µL, 0.144 mmol) Nas treated Nith sodium triacetoxyborohydride (37 mg, 0.173 mmol) and stirred at ambient temperature for 10 min. The reaction mixture Nas applied directly to SGX resin, eluting non-basic compounds Nith MeOH and the basic compounds Nith 1N ammonia in MeOH. The basic Nashings Nere concentrated in vacuo and purified by flash column chromatography on silica gel eluting Nith DCM : MeOH: Q.8B0 ammonia (1:0:0 changing to 40 : 10 : 1, by volume) further purification on reverse phase silica eluting Nith Nater : acetonitrile (1 : 0 changing to 19:1 by volume) gave the title compound as a Nhite solid (14 mg, 35%). 1H NMR (400MHz, CD3OD): 5 7.9 (1H, s), 5.4 1H, s), 4.2 (1H, m), 3.2 (2H, m), 2.9 (1H, m), 2.8 (1H, m), 2.5 (2H, m), 2.4 (4H, m), 1.7 (1H, m), 1.5 (2H, m) 1.1 (9H, s) ppm. MS (APCI) m/z 278 [M+H]+, 276 [M-H]" Example 9: N4-(Cvclopropvlmethvl)-6-[(3R)-3-(methvlamino)pvrrolfdin-1-vnpvrimidin6-2.4-diamine (Formula Removed) A solution of the compound of preparation 15 (120 mg, 0.38 mmol) in NMP (2 mL) Nas treaied Nith DIPEA (191 µL, 1.1 mmol) and 1-cydopropylmethylamine (99 µL, 1.15 mmol) and heated to 150 °C in a sealed vessel for 18 hours. The reaction mixture Nas diluted Nith ethyl acetate (50 mL) and Nashed Nith Nater (4 x 50 mL) and saturated aqueous sodium chloride (50 mL), dried (MgSO4) and concentrated fri vacuo to give the crude intermediate tret-butyloxycarbonyl-protected compound. This crude material Nas dissolved in DCM (2 mL), treated Nith trifluoroacetic acid (2 mL) and stirred at ambient temperature for 3 h Nter Nhich time the reaction mixture Nas concentrated in vacuo. The residue Nas purified directly by SCX resin, eluting non-basic compounds Nith MeOH and the basic compounds Nith 2 N ammonia in MeOH. The basic Nashings Nere concentrated in vacuo and purified by flash column chromatography on silica gel eluting Nith DCM: MeOH : 0.880 ammonia (1:0:0 changing to 170: 30 : 3, by volume) to yield the title compound as a Nhite foam (16 mg, 17%). 1H NMR (400MHz, CD3OD): 5 4.89 (1H, s), 3.63 (1H, m), 3.55 (1H, m), 3.47 (1H, m}, 3.39 (1,H, m), 3.23 (1H, m), 3.05 (2H, d), 2.42 (3H, s), 2.21 (1H, m), 1.88 (1H, m), 1.06 (1H, m), 0.52 (2H, q), 0.23 (2H, q) ppm. MS (APCI) m/z 248 [M+H]+ Alternative method for example 9: N4-{CvcloDropvlmethYl)-6-[(3R)-3-(methylamino)pvrrolidin-1-vllpvrimidin6-2,4-diamine (Formula Removed) A suspension of the compound of preparation 15 (1.8g, 5.5mmal) in cyclopropylmethanamine (5.4ml, 62.3mmol) and TEA (1.53ml, 11 mmol) Nas heated in a sealed pressure vessel at 120DC for 24 hours. The excess amine Nas removed in vacuo and the residue partitioned betNeen Nater (100ml) and DCM (100ml). The aqueous phase Nas separated and extracted Nith further DCM (100ml). The combined organic extracts Nere Nashed Nith saturated aqueous sodium chloride (100ml) and the solvent removed in vacuo. Purification by flash column chromatography on silica gel eluting Nith DCM : MeOH : 0.880 ammonia (98 : 2 : 0 changing to 95 : 5 ; 0.2, by volume) gave the to give the intermediate tert-butyloxycarbonyl-protected compound (1.55g, 77%). ''H NMR (400MHz, CD3OD): 5 4.89 (1H, s), 4.71 (1H, m), 3.64 (2H, m), 3.32 (2H, m), 3.07 (2H, d), 2.80 (3H, s), 2.13 (2H, m), 1.46 (9H, s), 1.05 (1H, m), 0.52 (2H, m), 0.23 (2H, m) ppm. MS (APCI) m/e 363 [M+H]+ A solution of the intermediate tert-butyloxycarbonyl-protected compound (6.18g, 16.6mmol) in methanol (15ml) Nas treated Nith 4M HCI in 1,4-dioxan (42ml, 168mmol) and the resulting solution Nas left to stir at room temperature (exotherm observed on addition of the HCI) for 18 hours. The solvent Nas removed in vacuo and the residue partitioned betNeen 0.880 ammonia (50ml) and DCM (400ml). The aqueous phase Nas separated and extracted Nith further DCM (200ml), The combined organic extracts Nere dried (sodium sulphate) and the solvent removed in vacuo to give a pale yelloN oif {4.00g, 92%). Example ,9a : N-(Cvc[opropvlmethvn-6-[(3R)-3-(methylamino)Dvrrollidin-1-vnpvrirnidin6-2.4-diamineL-tartrate (Formula Removed) A solution of the compound of example 9 (10.14g, 36.65mmol) in methanol (340ml) Nas treated Nith a solution of L(+) tartaric acid in (5.8g, 38.65mmol) in methanol (50ml). The resulting suspension Nas stirred at room temperature for 30 minutes and the resulting solid filtered off and dried in vacuo. The solid Nas dissolved in the minimum volume of boiling Nater (22mt) and then methanol Nas added until a permanent ppt Nas observed (102ml). The resulting suspension Nas alloNed to cool gradually to room temperature and the solid filtered and dried in vacuo for 50°C for 3 days and then alloNed to equilibrate at room temperature in air for a further 2 days to give the title compounds as a colourless solid (14.15g, 89%) ''H NMR (400MHz, CD3OD): 6 6.41 (1H, br s), 5.72 (2H, br s), 4.81 (1H, s), 3.92 (2Hr s), 3.58 (2H, m), 3.40 (1H, m), 3.32 (2H, m), 3.03 (2H, m), 2.48 (3H, s), 2.18 (1H, m), 1.95 (1H, in), 0.96 (1H, m), 0.39 (2H, m),0.12(2H,m)ppm. MS(APCI)m/z263[M+H]+ Examples 10 to 12 The folloNing compounds Nere prepared by a method similar to that described for example 9 using the title compound of preparation 15 and the appropriate amine starting materia!. (Table Removed) Examples 13 to 15 The foiioNing compounds Nere prepared by a method similar to that described for example 9, using the compound of preparation 10 and the appropriate amine starting material. (Table & Formula Removed) Examples 16 to 17 The folloNing compounds Nere prepared by a method similar to that described for example 9 using the compound of preparation 11 and the appropriate amine starting material. (Table & Formula Removed) Example 18: 6-](3R)-3-(Dimethvlamino)pvrrolidin-1-vl]-N-(3.3-dimethvlbutvl)Dvrimldin-4-amine (Formula Removed) A solution of the title compound of preparation 2 (120 mg, 0.53 mmol) in NMP (2 mL) Nas treated Nith DIPEA (276 µL 1.59 mmol) 3,3-dimethylbutan-1 -amine (213 µL, 1.59 mmol) and heated to 150 °C in a sealed vessel for 72 hours. The reaction mixture Nas cooled and purified directly by SCX resin, eluting non-basic compounds Nith MeOH and the basic compounds Nith 2 N ammonia In MeOH. The basic Nashings Nere concentrated in vacuo and purified by flash column chromatography on silica gel eluting Nith DCM : MeOH : 0.880 ammonia (1:0:0 changing to 40 : 10 : 1, by volume) to yield the title compound as a gum (72 mg, 47%). 1H NMR (400MHz, CD3OD): 5 7.92 (1H, s), 5.30 (1H, s), 3.72 (1H, m), 3-61 (1H, m), 3-37 (1H, m), 3.24 (2H, m), 3.17 (1H, m), 2.89 (1H, m), 2.32 (6H, s), 2.25 (1H, m), 1.87 (1H, m), 1.52 (2H, m), 0.98 (9H, s) ppm. MS (APCl) m/z 292 [M+H]+ Examples 19 to 22 The folloNing compounds Nere prepared by a method similar to that described for example 18 using the title compound of preparation 2. (Table & Formula Removed) Example 23: N -(3.3-DimethvlbutylV-6-Tf4aR*,7aR*)-octahvdro-6H-pyrrolor3,4-blpyrtdin-8- vllpyrimidin6-2,4-diamine (Formula Removed) The title compound of preparation 24 (45 mg, 0.11 mmol) Nas dissolved in trifluoroacetic acid (2 mL) and stirred at ambient temperature for 1 hour Nter Nhich time the reaction mixture Nas concentrated in vacuo. The residue Nas purified directly by SCX resin, eluting non-basic compounds Nith MeOH and the basic compounds Nith 1 N ammonia in MeOH taking 4 mL fractions to yield the title compound as a solid (25 mg, 71%). 1H NMR (400MHz, CD3OD): 8 3.52 - 3.33 (5H, m), 3.22 - 3.14 (2H, m), 2.97 - 2.86 (1H, m), 2.66 - 2.57 (1H, m), 2.40 - 2.29 (1H, m), 1.80 - 1.72 (2H, m), 1.70 - 1.55 (1H, m), 1.53 -1.43 (3H, m), 0.97 (9H, s) ppm, MS (ESI) m/z 319 [M+H]+ Example 24: N4-lsoproDVl-6-[(4aR*.7aR*)-octahvdro-6H-Dvrrolor3.4-blPvr3ciin-B-yl]pvrinidine-2,4-diamine (Formula Removed) The title compound was prepared by a method similar to that described for example 23 and preparation 24, by reaction of the compound of preparation 14 with isopropyi amine and subsequent deprotection, in 28% yield. 1H NMR (400MHz, CD3OD): 5 4.77 (1H, s), 3.86 - 3.74 (1H, m), 3.51 - 3.34 (5H, m) 2.96 - 2.86 (1H, m), 2.66 - 2.56 {1H, m), 2.40 - 2.26 (1H, m), 1.81 -1.72 (2H, m), 170 -1.57 (1H, m), 1.54 -1.41 (1H, m) 1.18 (6H, d) ppm MS (ESi) m/z 277 [M+Hf Examples 25 to33 The following compounds were prepared by a method similar to that described for example 23 and preparation 24 by reaction of the compound of preparation 14 with an appropriate amine and subsequent deprotection. (Table Removed) Example 34:6-[(3aR*.6aS*)-5-Methvlhexahvdropvrrolor3.4-c]pvrrol-2(1H)-vn-N4-propylpyrimfdine-2,4-diamine To a solution of the title compound of preparation 13 (20 mg, 0.08 mmol) in DMSO (75 µL) was added propylamine (75 µL, 1 mmol) and the mixture was heated to 120 °C in a sealed vessel for 48 hours. The reaction mixture was concentrated in vacuo to give a brown gum. The residual gum was purified by flash column chromatography on silica gei eluting with DCM: MeOH : 0.880 ammonia (990:10 :1 changing to 90 :10 :1, by volume) to yield the title compound as a gum (10 mg; 45%). 1H NMR (400MHz, CD3COCD3): 5 5.28 (1H, brt), 4.97 (3H, m), 3.51 (2H, m), 3.20 (4H, m), 2.83 (H, m), 2.51 (2H, m), 2.41 (2H, m), 2.22 <3H, s) 1.56 (2H, m), 0.92 (3H, t) ppm MS (ESI) m/z 277 [M+H]+ Examples 35 to 43 The following compounds were prepared by a method similar to that described for example 34 using the compound of preparation 13 and the appropriate amine starting material. (Table Removed)A solution of the title compound of preparation 22 (70 mg, 0.21 mmol) in DCM (5 mL) Nas treated Nith trifluoroacetic acid (0.5 mL) and stirred at ambient temperature for 2 hours Nter Nhich time the reaction mixture Nas concentrated in vacuo. Th6- residue Nas purified directly by SCX resin, eluting non-basic compounds Nith MeOH and the basic compounds Nith 2 N ammonia in MeOH taking 20 ml fractions to yield the title compound (45 mg, 92%). 1H NMR (400N!Hz, CDCI3): S 8.12 (1H, s), 5.06 (1H, s), 4.89 (1H, br s), 4.20 (2H, m) 3.71 (3H, m), 3.03 (2H, m), 2.42 (3H, s), 1.05 <1H, m), 0.54 (2H, m), 0.24 (2H, m) ppm. Accurate mass: found 234.1709, C12H2oN5 requires 234.1719. Example 45: (3-Fluoro-benzvlH6-(3-methvlamino-azetidin-1 -vl)-Dvrimidin-4-vl1-ann!ne (Formula Removed) A solution of the title compound of preparation 23 (42 mg, 0.11 mmol) In DCM (5 mL) Nas treated Nith trifluoroacetic acid (0.5 mL) and stirred at ambient temperature for 2 hours Nter Nhich time the reaction mixture Nas concentrated in vacuo. The residual oil Nas purified by flash column chromatography on silica get eluting Nith DCM : MeOH : 0.880 ammonia (1.0:0 changing to 182 :15 : 3, by volume) to yield the title compound as a solid (29 mg, 94%). 1H NMR (400MHz, CDCI3): 5 8.17 (1H, s), 7.29 (1H, m), 7.09 (1H, d), 7.02 (1H, d), 6.97 (1H, rn), 5.07 (1H, d), 5.02 (1H, br s), 4.45 (2H, d), 4.16 (2H, m), 3.69 (3H, m), 2.42 (3H, s) ppm. MS (APCI) m/z 2B8 [M+H]+ Examples 46 to 59 The folloNing compounds Nere prepared by a method similar to that described for example 44 and preparation 22, by reaction of the compound of preparation 1 Nith an appropriate amine and subsequent deprotection. (Table Removed) Example 60: N4-lsooroDVl-6-(3-methvlamino-azetidin-1-vl)-Dvrimidin6-2.4-diamirie The title compound of preparation 26 (22 mg, 0.07 mmal) Nas dissolved in trifluoroacetic acid (1 mL) and stirred at ambient temperature for 2 hours Nter Nhich time the reaction mixture Nas concentrated in vacuo, The residual gum Nas purified by flash column chromatography on silica gel etuting Nith DCM ; NleOH : 0.B80 ammonia (98 : 2 : 0.2 changing to 90 :10 :1, by volume) to yield the title compound as a gum (''I2mg, 73%). ''H NMR (400MHz, CD3OD): S 4.74 (1H, s)., 4.1 (2H, dd), 3.82 (1H, m), 3.67 {2H, m), 3.61 (1H, m), 2.33 (3H, s), 1.16(6H,dl)ppm. MS(APCI)m/z237[M+H]+ Example 61: N4-(2.2-Dimethvlpropvl)-6-F3-(methvlamino)a2etidin-1-vl]pyrimidin6-2.4-diamine (Formula Removed) The title compound Nas prepared by a method similar to that described for example 60, using the compound of preparation 25, in 91% yield. ''H NMR (400MHz, CD3COCD3): 5 5.29 (1H, brt), 4.97 (2H, br s), 4.79 {1H, s), 3.97 (2H, t), 3.56 - 3.49 (3H, m), 3.08 (2H, br d), 2.32 (3H, s), 0.93 (9H, s) ppm MS (ESI) m/z 265 [M+H]+ Example 62: 6-(3-Methvfamino-azetidlrt-1 -vn-N4-(3,3,3-trifluoro-propvl)-Pvrimidin6-2,4-diamine (Formula Removed) The title compound Nas prepared by a method similar to that described for example 6D, using the compound of preparation 27, in 92% yield. "H NMR (400MHz, CD3OD): 5 4.7S (1H, s), 4.11 (2H, m), 3.68 (2H, dd), 3.62 (1H, m), 3.45 (2H, t), 2.42 (2H, m), 2.34 (3H, s) ppm MS (ESI) m/z 291 [M+H]+ Example 63: N4-Cvc[oproDvlmethvl-6-(3-methvlamino-azetidin-1-yl)-pvrimidin6-2.4-diamine The title compound Nas prepared by a method similar to that described for example 60, using trie compound of preparation 28, in 85% yield. ''H NMR (400MHz, CD3OD): & 4.17 (2H, m), 3.76 (2H, m), 3.70 (1H, m), 3.06 (2H, d), 2.39 (3H, s), 1.01 (1H, m), 0.52 (2H, m), 0.22 (2H, m) ppm. MS (APCI) mfe 249 [M+H]+ Example 64: N4-{3.3-DimethyUbutvlV6-(3--rnethvlamino-azetldin-1-vB-pvrimidin6-2.4-cliamme (Formula Removed) The title compound Nas prepared by a method similar to that described for example 60, using the compound of preparation 29, in 87% yield. 1H NMR (400MHz, CD3OD): 5 4.73 (1H, s) 4.11 (2H, m}, 3.68 (2H, m), 3.62 (lHr m), 3.1 B (2H, m), 2.33 (3H, s), 1.48 {2Hf m), 0.96 <9H, s) ppm. MS (APCI) m/z 279 [M+H]+ Example 65: M4-(3-Fluoro-benzvn-6-(3-methvlamino-azetidin-1-yl)-pyrimidin6-2,4-diamine (Formula Removed) The title compound Nas prepared by a method similar to that described for example 60, using the compound of preparation 30, in 84% yield. 1H NMR (400MHz, CD3COCD3): 5 7.32 (1H, m), 7.16 (1H, d), 7.10 (1H, br d), 6.96 (1H, m), 6.01 (1H, m), 5.06 (2H, tors), 4.79 (1H, s), 4.51 (2H, d), 3.96 (2H, t), 3.57 - 3.48 (3H, m), 2.31 (3H, s) ppm. MS (APCI) m/z 303 [M+H]+ Example 66: N4-(3-lUlethoxv-bertzyn-6-(3-inethvlamlno-azetldin-1-vH-Dvr?midin6-2.4-dlainine The title compound Nas prepared by a method similar to that described for example 60, using the compound of preparation 31, in 72% yield. 1H NMR (400MHz, CD3OD): 8 7.20 (1H, t), 6.89 - 6.85 (2H, m), 6.78 (1H, dd), 4.73 (1H, s), 4.37 (2H, s), 4.07 (2H, t), 3.76 (3H, s), 3.65 - 3.55 (3H, m), 2.31 {3H, s) ppm. MS(APCl)m/z315[M+H]+ Example 67: N4-Cvclobutvlmethvl-6-(3-methylamino-azetidin-1-vn-pvrimidine-2.4-diamine (Formula Removed) The title compound Nas prepared by a method similar to that described for example 60, using the compound of preparation 32, in 86% yield. 1H NMR {400MHz, CD3COCD3): 8 5.31 (1H, m>, 4.99 (2H, br s), 4.73 (1H, s), 3.96 (2H, t), 3.58-3.50 (3H, m), 3.23 (2H, t), 2.55 (1H, m), 2.32 (3H, s), 2.05 - 1.97(H, m), 1.90-1.82 (2H, m), 1.77 -1-66 (2H, m) ppm. MS(APCI)rn/z263fM+Hf Example 68: N4-Cvclopentvlmethvl-6-(3-methvlamino-azetldm-1-vH-pyrimldm6-2.4-diamfne (Formula Removed) The title compound Nas prepared by a method similar to that described for example 60, using the compound of preparation 33, in 81% yield. ''H NMR (400MHz, CD3OD): 5 4.75 (1H, s), 4.11 (2H, dd), 3.68 (2H, dd), 3.61 (1H, m), 3.09 (2H, d), 2.33 (3H, s), 2.13 (1H, rn), 1.83 -1.75 {2H, m), 1.70 -1.53 (4H, m), 1.29 - 1.21 (2H, m) ppm. MS (APCI) m/z 277 [M+H]+ Examples 69 to 90 The folloNing compounds Nere prepared by a method similar to that described for example 60 and preparation 26 by reaction of the compound of preparation 12 Nith an appropriate amine and subsequent deprotection. (Table Removed) Example 91: N -(3-FluorobenzvlV6-(4-methvlpiperazin-1-vl''iPvrimidin6-2.4-diamine (Formula Removed) The title compound of preparation 13 (20 mg, 0.08 mmol) Nas treated Nith DMSO (150 µL) and N-methylpiperazine (88 µL, 0.79 mmol) and heated to 120 °C in a sealed vessel for 16 hours. The reaction mixture Nas cooled to ambient temperature, partitioned betNeen Nater (2 mL) and ethyl acetate (2 mL) and filtered through diatomaceous earth, Nashing Nith further ethyl acetate (15 mL). The organic fraction of the filtrate Nas concentrated in vacuo and purified by flash column chromatography on silica gel eluting Nith DCM : MeOH : 0.880 ammonia (90 :10 : 1 changing to 90 :10 : 1, by volume) to yield the title compound as a gum (20 mg, 79%). 1H NMR (400MHz, CD3OD). B 7.34 - 7.27 (1H, m), 7.14- 7.10 (1H,m), 7.0B -7.01 (1H, m), 6.98 -6.89 (1H, m), 5.11 (1H, s), 4.45 (2H, s), 3.51 ■■ 3.42 (4H, m), 2.48 - 2.41 (4H, m), (2.30 (3H, s) ppm. MS (APCt) m/z 208 [M-C7H6F,+2H]+ Examples 92 to 98 The folloNing compounds Nere prepared by a method similar to that described for example 91 using the appropriate pyrimidine starting material and the appropriate amine starting material. (Table & Formula Removed) Examples 128 to 132 The folloNing compounds Nere prepared by a method similar to that described for example 60 and preparation 26 by reaction of the compound of preparation 12 Nith an appropriate amine and subsequent deprotection. (Table & Formula Removed) The folloNing compounds Nere prepared by similar method to those used to prepare the compounds above, using the appropriate pyrimidine starting material and the appropriate amine: Example Name 154 N4-(Cyclopropylmethyl)-6-piperazin-1 -yJpyrirnidin6-2,4-diamine 155 N4-(4-Fluorobenzyl)-6-[(3R)-3-(methylamino)pyrrolidin-1-yl]pyrimidin6-2,4-diamine 156 N4-(2,2-Dimethylpropyl)-6-piperazin-1-ylpynmidin6-2,4-diamine 157 N4-(2,4-Difiuorobenzyl)-6-[3-(methylamino)azetidin-1-yl]pyrimidin6-2,4-diamine 158 6-[3-{Methylamino)azetidin-1-yl]-N4-(1-methylbutyl)pyrimidin6-2,4-diamine 159 N4-(2,2.-Dimethy!propyl)-6-[3-.(methy!amino)azetidin-1-yl]pyrimidin6-2,4-diamineriydroch!oride 160 N4-[(1 R)-1,2-Dlmethylpropyl]-6-[3-(methylarnino)azetidin-1 -yl]pyrimidin6-2,4-dlamine 161 6-[3-(Methy]amino)azetidin-1-yi]-N4-[(1S)-1-methy]propyl]pyrimidin6-2,4-diamine N4-(2,2-Dimethylpropyl)-6-[(3aR*,7aS*)-octahydro-5H-pyrrolo[3,2-c]pyridin-5-yl]pyrimidin6-2,4-162 diamine 163 6-Piperazin-1 -yl-N4~propylpyrimidin6-2,4-diamine 164 N4-Ethyl-6-[3-(methylamino)azetidin-''i-yl]pyrimidin6-2,4-diamine N4-(Cycloprapylmethyl)-6-[(4Nl,7aR)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]pyr3midiri6-2,4-165 diamine N4-(2,2-Dimethy[propy!)-6-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-blpyridln-6-yl]pyrimidin6-2,4- ''i66 diamine 167 N4-{Cyc]opropylmethy))-6-[(3R)-3-(methylamino)pyrrolidin-1-yl]pyrimidin6-2,4-diamine 168 N4-(tert-Butyl}-6-[3-(methy!amino)azetidin-1-yl)pyrimidin6-2,4-diamtne 169 N4-|sopropyl-6-[(4aS,7aS)-octahydro-6H-pyrrolDt3,4-b]pyridin-6-yl]pyrimtdin6-2,4-diamine 170 6-(3-Amlnoazetidin-1-yl)-N4-eihylpyrimidin6-2,4-diamme 171 6-(a-Amlnoazetidin-1-yl]-N^-fcyclopropylmethyl]pyrimidin6-Z^-diamine 172 N4-Cyciopropyl-6-[(3aR*,7aS*)-octahydro-5H-pyrro[o[3,2-olpyridin-5-yl]pyrimidin6-2,4-diamine 173 4-[3-(Methylamino)azetidin-1-yl]-6-(4-methylpiperidin-1-yl)pyrimidin-2-amine 174 N4-(Cyclopenty[methyl)-6-[(3R)-3-{methylamino)pyrrolidin-1 -yl]pyrimidiri6-2,4-diarnine 175 B-(1,4-Diazepan-1 -yl)-N4-ethylpy rimidin6-2,4-diamine 176 N4-{Cyclopropylmethyl)-N6-[2-(dimethylamitio)ethyl]pyrimidin&-2,4,6-triarnine 177 N4-(2,2"Dimethylpropyl)-6-[(3S)-3--(methylamirio)pyrroIidin-1-yl]pyriiTiidin6-2,4-diamine 178 N4-Cyclobutyl-6-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]pyrimidin6-2,4-diamine 179 N-Cyclobutyl-6-[3-(methylamino)azetidin-1-yl]pyrimidin-4-amine 180 6-t(3R)-3-(Methylamino)pyrrolidin-1 -yl]-N4-propylpyrimidin6-2,4-diamine 181 N-Cyclobutyl-6-[(3R)-3-(methylamino)pyrrc)lidin-1-yl]pyrimidiri-4-amine 182 N4-(2-Methoxyethyl)-6-[3-(methylamino)azetidin-1-yl]pyrimidin6-2,4-diamine 183 N-(2,2-Dimethylpropyl)-6-[(3R)-3-(methylamino)pyrrQlidin~1-yl]pyrimidirt-4-amine 184 N4-(Cyclopropylmethyl)-6-[(3S)-3-methyl piperazin-1 -yl]pyrlmidin6-2,4-diamine 185 N4-Ethyl-6-(4-methyl-1,4-diazepan-1 -yl)pyrimidin6-2,4-diamine 186 N4-{2,2-Dimethylpropyl)-6-[3-methyl-3-(methylamino)azetidin-1 -yl]pyrimidin6-2,4-diamine 1B7 N4-lsopropyl-6-piperazin-1-ylpyrimidin6-2,4-diatriine N4-(Cyclopropylm6thyl)-6-K3aR*,7aS*)-octahydro-5H-pyrrolol[3,2-clpyridin-5-yl]pyrimidin6-2,4-188 diamine 189 NI-Cydopropyl-6-[3-(methylamino)azetidin-1-yl]pyrimidin-4-amine 190 6-{3-Aminoazetidin-1-yl)-N4-(2,2-dimemylpropyl)pyrimidin6-2,4-diamine N4-(2,2-Dimethylpropyl)-6-[(1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl]pyrimidin6-2,4-diamine 192 N-(2,2-Dimethylpropyl)-6-(3-pyrrolidin-1 -ylazetidin-1-yl)pyrirrudin-4-amine 193 N4-Ethyl-6-[(3aR*7aS*)-octahydro-5H-pyrrolo[3,2-clpyridin-5-yl]pyrimidine2,4-diamine 194 N-(Cyclopropylmethyl)-N''-l2-(dimethylamino)ethyl]pyrimidin6-4,6-diamine 195 6-[(3R)-3-Aminopyrrolidin-1 -yl]-H'',-(2-mettiylbutyi)pyrimidin6--2,4-diamine 196 N4-(Cyclopropy[methyl)-6-{3-methyl-3-(methylamina)azetldin-1-yilpyrimidin6-2,4-diamine 197 N4-Ethyl-6-(3-pyrrolidin-1 -ylazetidin-1 -yl)pyrimtdin6-2,4-diarnine 198 N4-isoPropyl-6-(4-methyl-1,4-diazepan-1-yl)pyrimidin6-2,4-diamine 199 IN4-Cyclobutyl-6-I(3R)-3-(methylaimino)pyrrolidin-1-yl]pyrimidin6-2,4-diamine 200 N^NIethyl-6-[(3aR*7arS*)-octahydro-5H-pyrrolo[3,2-clpyridin-5-yl]pyrimidine2,4-diamine 201 6-(4-Arninopiperidin-1-yl)-N4-(2,2-dimethylpropyl)pyrimidin6-2,4-diannine 202 N-lsopropyl-6-[(3R)-3-(methylamino)pyrrolidin-1 -yi]pyrimldin-4-amine 203 N-Cyclopropyl-6-[(3R)-3-(methylamino)pyrrolidin-1-yl]pyrimidin-4-amine 204 N4-(Cyclopropylmethyl)-6-[(3S)^-(methySamino)pyrrolidin-1-yl]pyrimidine"2,4-diamine 205 N4-Ethyl-6-[(3S)-3-(methylamino)pyrrolidin-1-yl]pyrimidin6-2,4-diamine 206 6-[3-(Methylamino)azetidin-1-yl]-N-propylpyrimtdin-4-amine 207 N^ffe/t-Birtyl]-6-tCSSJ-S^metliylamirioJpyrroIidin-1-yl]pyrirriidine2,4-diamine 20S N4-Methyl-6-piperazin-1-ylpyrimidin6-2,4-diamine 209 N4-(2,2-Dimethylpropy!)-6-{3-[(metlnylamino}methyl]azetidiri-1-yl}pyrimidiri6-2,4-d!amine N4-(Cyclopropylmethyl)-6-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]pyrimidin6-2,4-diamine 211 N4-{3,3-Dimethylbuty!)-6-[(3S)-3-(meyiylamino)pyrrolidin-1 -yi]pyrimidin6-2,4-diamine 212 N4-(2-Aminoethyl)-N4l-(cyclopropylmethyl)pyrimidin6-2,4,B-triannine 213 N4-(2-Fluorobenzyl)-6-[(3S)-3-methylpiperazin-1 -yl]pyrimidin6-2,4-diamine 214 N4-Ethyl-6-piperazin-1 -ylpyrimidin6-2,4-diamine 215 6-[(3R)-3-Aminopyrrolidin-1 -yl]-N4-(cyclopropy)methy!)pyrimidin3-2,4-diamine 216 6-[(3R)-3-Aminopyrrolidin-1-yl]-N4-isobutyIpyrimidin6-2,4-diamine 217 6-[(3aR*6aS*)Hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]-N4-isobutylpyrimidine-2,4-diamine 218 6-[(3R)-6-Aminopyrrolidin-1-yl)-N4-Ccyclopentylmethyl)pyrimidin6-N-diannlne 219 6-[(3R)-3-Aminopyrrolidin-1-yl]-N4-propylpyrimldin6-2,4-diamine 220 N-(2-Am1noethyl)-N''-(cyclopropylmethyl)pyrimidin6-4,6-diamine 221 N4-Methyl-6-[(3R)-3-(methy]amino)pyrrolidin-1-yl]pyrimidin6-2,4-diamine N4-[(1R*,5S*,6s*)-3-Azabicyclo[3.1.01hex-6-yl]-N4-(2,27dimethylpropyl)pyrim(din6-2,4,6-triamlne 223 IN4-(fert-Butyl)-6-(4-methylpiperazin-1-yI)pyrimidin6-2,4-diainirie 224 N-Cydopropyl-6-(4-methyf-1,4-diazepan-1-yl)pyrimidiri-4-amine 225 6-[(3R)-3-Aminopyrrolidln-1-yl]-N4-(3,3-dimethylbutyl)pyrimidiri6-2,4-diamirie 226 N-(2,2~Dimethylpropyl)-6-[3-{isopropyIamino)azelidin-1-yl]pyrimidin-4-amine 227 N4e 346 N-(2-Phenylethyl)-N''-[(3R)-pyrro!idin-3-yI]pyrimldin6-4,6-diamine 347 N-(Cyclopropylrnethyl)-N''-[2-(methy]amino}ethyl]pyrimidtn6-4,6-d''ianilne 348 N-[(3R)-1-Benzylpyirolidln-3-yl]-N''-(3,3-dimethylbutyl)pyrimidine-4,6-diamine {54[(3R)-3-({6-[(3,3-Dimethylbutyl)amino]pyrimidin-4-yl}amino)pyrrolidiri-1-yl]metfiyl}-2-furyl)methanol 350 N-(2,3-Dihydro-1H-inden-2-yl)-N-(3R)-pyrrolidin-3-yl]pyrimidin6-4,6-diarnine 351 6-(3,4-Dihydroisaquinolin-2(1H)-yl)-N-K3R)-pyrrolidin-3-yl]pyrimidin-4-amine 352 N4-(3-Ffuorobenzyl)-6-[3-{methylamino)azet1din-1-yl]pyrlm]din6-2,4-diamlne N-(2,2-Dimethylpropyl)-6-[(1R,5S)-1,2,4,5-tetrahydro-3H-1,5-epimino-3-benzazepitv3-353 yl]pyritnidin-4-amine 354 N4-Cyclobutyl-6-[{4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]pyrimidin6-2,4-diamine N4-(Cyclopropylmethyl)-6-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyrldin-6-yl]pyrimidin6-2,4-355 diamine 356 N'',-(tret-Butyl)-6-(4-methylpiperazin-1-yl)pyrimidin6-2,4-diamine 357 N4-(tert-Butyl)-6-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]pyrimidin6-2,4-diamirie N4-(2,2-Dimethy]propyl)-6-[(1 R*,5S*,6s*)-6-(metliylamino)-3-azabicyclo[3.1.0]hex-3-358 yl]pyrimidine2,4-diamine 359 N4-Cyclopropyl-6-[{4aR,7aR)-octahydro-6H-pyrrolot3,4-b]pyridin-6-yl]pyrinnidine-2,4-diarnine 360 2.({2-Amino-6-[3-{methylamino)azetidin-1-yl]pyrimidin-4-yl}amino)ethanol 361 6-(1,4-Diazepan-1-yl)-N4-isopropy]pyrimidin6-2,4-diamine 362 6-[(1R,4R)-2,5-Diazabicyc)o[2.2.1]thept-2-yl]-N4-(2,2-dimethylpropyl)pyrirnidin6-2,4-diamine 363 6-[(3R)-3-Aminopyrroridin-1-yl]-N4-(2,2-dimethylpropyl)pyrimidine-2,4-diamme 364 4-[(3R)-3-{Melhylamino)pyiTolidin-1 -yl]-6-(2-methyl-1H-imidazol-1 -yl)pyrimidin-2-amine 365 6-[3-(Methylamino)azetidin-1-yl3-N4-[(i R)-1 -methylpropyl]pyrimidin6-2,4-diamine 366 6-[(3R)-3-Aminopyrrolidin-1-yl]-N4-ethylpyrimidin6-2,4-diamine 367 6-[(3R)-3-Aminopyrrolidin-1-yl]-N4-(3l3,3-trifluoropropyl)pyrimidin6-2,4-diamine 366 6-[(3R)-3-{Nlethylamino)pyrroliditi-1 -yl]-N-[(1 S)-1-methylpropyl]py rimidin-4-amine 369 6-[3-(Methylamino)azetidin-1 -ylI-N-[(1 R)-1-methylpropyl]pyrimidin-4-amine 370 6-[(3R)-3-{Methylamino)pyrrolidin-1-yI]-N-propylpyrimidin-4-amine 371 6-(3-Aminoazetidin-1-yl)-N-(2,2-dimethytpropyl)pyrimidin-4-amme 372 N4-(Cyclopropylmethyl)-5-methyl-6-[(3R)-3-(methylamino)pyrrolidin-1-yi]pyrimidin6-2,4-diarmine 373 N4-(Cycloprapylmethyl)-6-(2,8-diazaspiro[4.5]dec-2-yl)pyrimidin6-2,4-diamine 374 6-(2,8-Diazaspiro[4.5]dec-2-yl)-N4-isobutylpyrimidin6-2,4-diamine 375 N4-(Cydopropylmethyl)-6-{2,7-diazaspiro[4.4]non-2-yl)pyrEmidin6-2,4-diamine 376 6-(2,7-Diazaspirol4.4]non-2-yl)-N4-isobuty)pyrimidin6-2,4-diamine Biology Hi Binding Cell pellets from CHO cells expressing the histamine H4 receptor Nere homogenised in ic6-cold 50mM Tri3-HCI/0.5mM CaCl2 buffer containing a protease inhibitor cocktail (Roche®, United Kingdom) using a ground glass homogeniser. Homogenates Nere centrifuged at 480Q0g for 30min at 4°C. The membrane pellet Nas resuspended In fresh buffer and the centrifugation step Nas repeated as described above. The membrane pellet Nas resuspended in 50mM Tri3-HCI in the same volume as the original cell pellet. Aliquots of membrane preparations Nere stored at -80°C and Nere used for [3H]-Histamine binding experiments. Method 1 Cell membranes (20-35µg/Nell) Nere incubated for 90 minutes shaking at room temperature Nith 3nM [2,5-3H]1-istamine dihydrochloride (30-60Ci/rnrnol) in 50mM Tri3-HCI (pH 7.4), Nith or Nithout competing H., ligands. The reaction Nas terminated by rapid filtration through 0.5% polyethylenimin6-soaked Unifilter GF/B plates (Packard) folloNed by three Nashes Nith 1 ml ic6-cold 50mM Tri3-HCI. Filters Nere dried for 45min at 45°C and bound radioiabel Nas determined using scintillation counting techniques. Non-specific binding Nas defined Nith 10µM JNJ7777120. For competition binding studies, Ki values Nere calculated from the IC50 value based on an experimentally determined ligand Kd of 5.2nM and a ligand concentration of 5nM according to the Cheng-Pmssoff equation Nhere; K1 = (IC50)/(1+(lL-l/Kd)). Method 2 Cell membranes (15ng/Nell) Nere pr6-incubated for 120min shaking at 4°C Nith Ysi NGA beads (250ng/Nell) In 50mM Tri3-HCI