The present invention relates to the process of reduction of compound of formula (II) by using a transition metal complex (Z) as a catalyst for hydrogenation reactions to get compound of formula (I). More particularly, the present invention relates to the use of palladium (Pd) complex (Z1) as a catalyst for hydrogenation reactions.

BACKGROUND OF THE INVENTION:

The following discussion of the prior art is intended to present the invention in an appropriate technical context, and allows its significance to be properly appreciated. Unless clearly indicated to the contrary, reference to any prior art in this specification should not be construed as an expressed or implied admission that such art is widely known or forms part of common general knowledge in the field.

Transition metal complexes are extensively studied by scientists worldwide for the implication in various chemical transformations; hence there is a rapid development of newer process technologies relevant to industrial scale reactions for the production of organic compounds using transition metal complexes as catalyst. It is also observed that the advanced research has been conducted globally in terms of formation of novel transition metal complexes as well as the use of known metal complexes as catalysts for critical chemical transformations.

Journal of Molecular Catalysis A: Chemical, 269, 218-224 (2007) discloses sulfonamide and hydrazine -based palladium catalysts (as depicted below as compound (D3)), for effective use as catalysts for C-C coupling reactions. The article explicitly discloses the utility of palladium complex for the Suzuki coupling of 4-bromotoluene with phenylboronic acid.

U.S. Patent No. 7,999,112 (hereafter US'112) describes a reusable transition metal complex catalyst useful for the preparation of high quality 3,3 '-diaminobenzi dine and its analogues, comprises homocoupling of substituted 4-halo-2-nitroaniline in the presence of a transition metal complex catalyst. US’112 discloses through its specification the homocoupling of substituted 4-halo-2-nitroaniline using a palladium metal complex catalyst, in the presence of an organic base, as depicted in below scheme (i).

Scheme (i)

There are several other metal complexes reported in the art such as, Coordination Chemistry Reviews, 250, 1980-1999 (2006) discloses certain saccharin based [M(sac)2(H20)4]*2H20 complexes (M = V, Cr, Mn, Fe, Co, Ni, Cu and Zn), also the article does not suggest the palladium (Pd)- saccharin complex. The compound as per Coordination Chemistry Reviews 2006 is depicted below as compound (D4);

Compound (D4)

Tikrit Journal of Pure Science 22 (2) 2017 describes synthesis and studies of Pd(II)-NHC complexes with thiosaccharinate, saccharinate or benzothiazolinate ligands as depicted below compound (D1):

Compound (D1)

In general, the catalytic hydrogenation has extensively been followed in the organic synthesis. The routinely demonstrated hydrogenation reactions are performed in the presence of a metal catalyst, such as Pd/C, Raney Nickel, platinum and others. Some of the reported hydrogenation reactions on the substrate of interest of the instant invention, which has a reducible functional group, are discussed herein.

J. Org. Chem. 71, 5921-5929 (2006) and J. Org. Chem. 81, 9046-9074 (2016) refer to the synthesis and resolution of 2,2'-, 4,4'-, and 6,6'-substituted chiral biphenyl derivatives for application in the preparation of chiral materials; wherein the articles disclose a method for preparing 2-amino-3-methyl-benzoic acid by reduction of the corresponding nitro compound in presence of Pd/C-th at 500 psi (about 35 kg/cm2) pressure, as depicted below scheme (ii):

scheme (ii)

In addition to afore discussed literature documents, there are a number of published patent and non-patent documents available that describe different metal complexes such as Bull. Chem. Soc. Jpn. 43, 3480 (1970), Oriental Journal of Chemistry, Vol. 35(1), 186-192 (2019); Inorganica Chimica Acta 56, L31 (1981), Journal of Thermal Analysis and Calorimetry vol 53 (3), p843-854 (1998); Journal of Bangladesh Academy of Sciences Vol. 37(2), pl95-203 (2013), similarly Chinese patent application CN 103373972.

It is evident from the above discussion that several transition metal complexes including palladium metal complexes are reported in literature and those are being extensively used for coupling reactions. However, the above referred literature documents do not mention the use of transition metal complexes, precisely palladium complex catalysts for hydrogenation reactions.

It is further evident that the traditionally reported metal catalysed hydrogenations as discussed above in presence of such as Pd/C, Raney Nickel, platinum are performed in an autoclave under high pressure. Some of the reported processes primarily provide products with low purity and yield, which involve critical reaction conditions, biphasic separations, purification using column chromatography, critical work up procedures and requires special technical instruments such as autoclaves; which renders the process costlier and hence the processes are not industrially feasible.

In view of these drawbacks, there is a need to develop an industrially viable commercial process for the hydrogenation of substrates having a reducible functional group; which is a simple, efficient and cost-effective process and provides the desired compounds in improved yield and purity.

Inventors of the present invention have developed an improved process that addresses the problems associated with the processes reported in the prior art. The present invention relates to the use of transition metal complex (Z) (as described herein) as catalyst for hydrogenation reactions. More particularly, the present invention relates to the use of palladium (Pd) complex (Z1) as catalyst for hydrogenation reactions, which provide chemical intermediates, agrochemical compounds as well as pharmaceutical compounds. The process of the present invention does not involve the use of any toxic and/or costly solvents and reagents. Moreover, the process does not require a specified instrumental set up, additional purification steps and critical workup procedures. Accordingly, the present invention provides a process for the hydrogenation of a substrate which has a reducible functional group, which is simple, efficient, cost effective, environmentally friendly and commercially scalable for large scale operations.

OBJECTIVE OF THE INVENTION:

The main objective of the present invention is to provide an improved hydrogenation process of compound of formula (I) using transition metal complex compound (Z).

Another objective of the present invention is to provide an improved hydrogenation process of compound of formula (IA) using transition metal complex compound (Z).

Yet another objective of the present invention is to provide a transition metal complex (Z) for catalyzing the hydrogenation reactions.

Yet another objective of the present invention is to provide a palladium complex compound (Z3) for catalyzing the hydrogenation reactions.

SUMMARY OF THE INVENTION:

In one aspect, the present invention relates to the process of reduction of compound of formula (II) by using a transition metal complex (Z) as a catalyst for hydrogenation reactions to get compound of formula (I).

transition metal complex (Z)

Hydrogen Source

Scheme-1

wherein,

R1 is a reducible functional group selected from the group consisting of -NO2, -CN, - CH=N-RZ and =N-RZ; provided when R1 represent =N-RZ then, one of the group from R3, R4 or R5 is absent;

R2 is selected from the group consisting of -Nth, -NH-RZ, -CH2NH2 and -CH2-NH- Rz;

R3, R4 and R5 are independently selected from the group consisting of hydrogen, Ci- Cio-alkyl, C2-Cio-alkenyl, C2-Cio-alkynyl, -C(=0)(0)o-iRx and C3-Cio-cabocylyl; or

R3 and R4 or R3 and R5 or R4 and R5 together with the atom they are attached form C3- Cio-carbocyclic/heterocyclic ring wherein R3, R4, R5 and said ring may substituted with one or more R groups;

R is selected from the group consisting of hydrogen, halogen, Ci-C6-alkyl, C2-C6- alkenyl, C2-C6-alkynyl, Ci-C6-alkoxy, Ci-C6-haloalkoxy, Ci-C6-alkylthio, C1-C6- haloalkylthio, -COOH, -ester, -C(=O)(O)0-iRx, ORy, -SH, -CN, -NH2, -NH(CI-C6- alkyl), -N(Ci-C6-alkyl)2 and -NH-S02-Rz;

Rx is selected from the group consisting of hydrogen, Ci-C6-alkyl, C1-C6- haloalkyl and aryl;

Ry is selected from the group consisting of hydrogen, Ci-C6-alkyl, C1-C6- haloalkyl, -C(=0)(0)o-iRx and aryl;

Rz is selected from the group consisting of hydrogen, Ci-C6-alkyl, C1-C6- haloalkyl, ORy, -C(=0)(0)o-iRx and aryl.

In another aspect, the present invention relates to an improved process for the preparation of compound of formula (I) (as described herein) or a salt thereof; comprising hydrogenation of compound of formula (II) (as described herein) using transition metal complex catalyst (Z).

transition metal complex Hydrogen Source

(P)

Scheme-1A wherein,

R1 is a reducible functional group selected from the group consisting of -NO2, -CN, - CH=N-RZ; R, Rx, Ry and Rz are same as defined above;

R2 is selected from the group consisting of -NH2, -CH2NH2 and -CH2-NH-RX;

R is selected from the group consisting of hydrogen, halogen, Ci-C6-alkyl, C2-C6- alkenyl, C2-C6-alkynyl, Ci- C6-alkoxy, Ci-C6-haloalkoxy, Ci-C6-alkylthio, C1-C6- haloalkylthio, -COOH, -ester, -COORx, ORy, -SH, -CN, -NH2, -NH(Ci-C6-alkyl), - N(Ci-C6-alkyl)2 and -NH-S02-RX, wherein Rx and Ry are independently selected from the group consisting of hydrogen, Ci-C6-alkyl, Ci-C6-haloalkyl and aryl;

m = 0-5.

In one aspect, the present invention relates to the use of transition metal complex (Z) as a catalyst for hydrogenation reactions:

(M)n (X)n (A)n

(Z)

wherein M is a transition metal selected from Palladium (Pd), Platinum (Pt), Nickel (Ni), Copper (Cu), Cobalt (Co), Manganese (Mn), Vanadium (V), Zinc (Zn), Chromium (Cr), Cadmium (Cd), Rubidium (Rb), Lanthanum (La), Lead (Pb), Zirconium (Zr), Gold (Au), Mercury (Hg), Scandium (Sc) and Titanium (Ti),

X is a halogen selected from fluorine (F), chlorine (Cl), bromine (Br) and iodine (I), n= 1-10,

A is an organic moiety selected from substituted or unsubstituted alkyl, alkenyl, alkynyl, carbocycle, heterocycle, aryl, heteroaryl, mono or bicyclic aromatic, mono or bicyclic heteroaromatic, saccharin, saccharin derivatives.

In one aspect, the present invention relates to the use of palladium complex compound (Z1) as a catalyst for hydrogenation reactions:

(Pd)n (X)n(A)n

(Z1)

wherein X is a halogen selected from fluorine (F), chlorine (Cl), bromine (Br) and iodine (I), n= 1-10,

A is an organic moiety selected from substituted or unsubstituted alkyl, alkenyl, alkynyl, carbocycle, heterocycle, aryl, heteroaryl, mono or bicyclic aromatic, mono or bicyclic heteroaromatic, saccharin, saccharin derivatives.

Another aspect, the present invention relates to the use of a palladium complex compound (Z2) as a catalyst for hydrogenation reactions:

(Pd)n (X)n (Saccharin)n

(Z2)

wherein X is a halogen selected from fluorine (F), chlorine (Cl), bromine (Br) and iodine (I), n= 1-10.

In one aspect, the present invention relates to the use of (Pd)-saccharin complex compound (Z3) as a catalyst for hydrogenation reactions:

Pd (Cl)2 (Saccharin)2

(Z3)

In one aspect, the present invention relates to an improved process for the preparation of compound (I) (as described herein) or a salt thereof; comprising hydrogenation of compound (II) (as described herein) using palladium (Pd)- saccharin complex catalyst (Z3) and an hydrogen source.

In another aspect, the present invention relates to an improved process for the preparation of compound (I) (as described herein) or a salt thereof; comprising the steps of:

(1) reacting palladium chloride with saccharin to form palladium- saccharin complex catalyst (Z3);

(2) optionally, isolating the palladium- saccharin complex;

(3) treating compound (II) (as described herein) with a hydrogen source in the presence of palladium-saccharin complex obtained from step (1) or step (2).

DETAILED DESCRIPTION OF THE INVENTION:

Accordingly, the present invention relates to the use of transition metal complex (Z) as catalyst for hydrogenation reaction:

(M)n (X)n (A)n

(Z)

wherein M is a transition metal selected from Palladium (Pd), Platinum (Pt), Nickel (Ni), Copper (Cu), Cobalt (Co), Manganese (Mn), Vanadium (V), Zinc (Zn), Chromium (Cr), Cadmium (Cd), Rubidium (Rb), Lanthanum (La), Lead (Pb), Zirconium (Zr), Gold (Au), Mercury (Hg), Scandium (Sc) and Titanium (Ti),

X is a halogen selected from fluorine (F), chlorine (Cl), bromine (Br) and iodine (I), n= 1-10,

A is an organic moiety selected from substituted or unsubstituted alkyl, alkenyl, alkynyl, carbocycle, heterocycle, aryl, heteroaryl, mono or bicyclic aromatic, mono or bicyclic heteroaromatic, saccharin, saccharin derivatives.

The meaning of various terms used in the description, and precisely relevant to define the scope of the organic moiety (A), shall be illustrated as follows:

Alkyl, alkenyl, alkynyl, carbocycle, heterocycle, aryl and heteroaryl groups, as defined herein, are optionally substituted (e.g., "substituted" or "unsubstituted" alkyl, "substituted" or "unsubstituted" alkenyl, "substituted" or "unsubstituted" alkynyl, "substituted" or "unsubstituted" carbocyclyl, "substituted" or "unsubstituted" heterocyclyl, "substituted" or "unsubstituted" aryl or "substituted" or "unsubstituted" heteroaryl group). In general, the term "substituted", whether preceded by the term "optionally" or not, means that at least one hydrogen present on a group (e.g., a carbon or nitrogen atom etc.) is replaced with a permissible substituent, e.g., a substituent which upon substitution results in a stable

compound, e.g., a compound which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, or other reaction under normal conditions (temperature, pressure, air etc.). Unless otherwise indicated, a "substituted" group has a substituent at one or more substitutable positions of the group, and when more than one position in any given structure is substituted, the substituent is either the same or different at each position.

The term "alkyl", used either alone or in compound words such as "alkylthio" or "haloalkyl" or -N(alkyl) or alkylcarbonylalkyl or alkylsuphonylamino or alkoxy or alkylsulfinyl includes straight-chain or branched Ci to Cio alkyl, more preferably Ci to Ce alkyl. Representative examples of alkyl include methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1 -ethyl- 1-methylpropyl and l-ethyl-2-methylpropyl or the different isomers. If the alkyl is at the end of a composite substituent, as, for example, in alkylcycloalkyl, the part of the composite substituent at the start, for example the cycloalkyl, may be mono- or polysubstituted identically or differently and independently by alkyl. The same also applies to composite substituents in which other radicals, for example alkenyl, alkynyl, hydroxyl, halogen, carbonyl, carbonyloxy and the like, are at the end.

The term "alkenyl", used either alone or in compound words includes straight-chain or branched C2 to Cio alkenes, more preferably C2 to Ce alkenes. Representative examples of alkenes include ethenyl, 1-propenyl, 2-propenyl, 1-methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1 -methyl- 1-propenyl, 2-methyl-l-propenyl, l-methyl-2 -propenyl, 2-methyl-2-propenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1 -methyl- 1-butenyl, 2-methyl- 1-butenyl, 3 -methyl- 1-butenyl, l-methyl-2-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl-3-butenyl, l,l-dimethyl-2-propenyl, 1,2-dimethyl- 1-propenyl, l,2-dimethyl-2 -propenyl, 1 -ethyl- 1-propenyl, l-ethyl-2-propenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1 -methyl- 1-pentenyl, 2-methyl- 1-pentenyl, 3 -methyl- 1-pentenyl, 4-methyl- 1-pentenyl, l-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-pentenyl, l-methyl-3-pentenyl, 2-methyl-3-pentenyl, 3-methyl-3-pentenyl, 4-methyl-3-pentenyl, l-methyl-4-pentenyl, 2-methyl-4-

pentenyl, 3-methyl-4-pentenyl, 4-methyl-4-pentenyl, l,l-dimethyl-2-butenyl, l,l-dimethyl-3-butenyl, 1,2-dimethyl-l-butenyl, l,2-dimethyl-2-butenyl, l,2-dimethyl-3-butenyl, 1,3-dimethyl- 1-butenyl, l,3-dimethyl-2-butenyl, l,3-dimethyl-3-butenyl, 2,2-dimethyl-3-butenyl,

2.3-dimethyl-l-butenyl, 2,3-dimethyl-2-butenyl, 2,3-dimethyl-3-butenyl, 3,3-dimethyl-l-butenyl, 3,3-dimethyl-2-butenyl, 1 -ethyl- 1-butenyl, l-ethyl-2-butenyl, l-ethyl-3-butenyl, 2-ethyl- 1-butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl, l,l,2-trimethyl-2-propenyl, 1-ethyl-l-methyl-2-propenyl, l-ethyl-2-methyl-l-propenyl and l-ethyl-2-methyl-2-propenyl and the different isomers. "Alkenyl" also includes polyenes such as 1,2-propadienyl and 2,4-hexadienyl. This definition also applies to alkenyl as a part of a composite substituent, for example haloalkenyl and the like, unless defined specifically elsewhere.

The term "alkynyl", used either alone or in compound words includes straight-chain or branched C2 to C10 alkynes, more preferably C2 to Ce alkynes. Non-limiting examples of alkynes include ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, l-methyl-2-butynyl, l-methyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-l-butynyl, l,l-dimethyl-2-propynyl, 1-ethyl -2-propynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, l-methyl-2-pentynyl, 1-methyl-3-pentynyl, l-methyl-4-pentynyl, 2-methyl-3-pentynyl, 2-methyl-4-pentynyl, 3-methyl-l-pentynyl, 3-methyl-4-pentynyl, 4-methyl-l-pentynyl, 4-methyl-2-pentynyl, 1,1-dimethyl-2-butynyl, l,l-dimethyl-3-butynyl, l,2-dimethyl-3-butynyl, 2,2-dimethyl-3-butynyl,

3.3-dimethyl-l-butynyl, l-ethyl-2-butynyl, l-ethyl-3-butynyl, 2-ethyl-3-butynyl and 1-ethyl-l-methyl-2-propynyl and the different isomers. This definition also applies to alkynyl as a part of a composite substituent, for example haloalkynyl etc., unless specifically defined elsewhere. The term "alkynyl" can also include moieties comprised of multiple triple bonds such as 2,5-hexadiynyl.

The term "cycloalkyl" means alkyl closed to form a ring. Non-limiting examples include but are not limited to cyclopropyl, cyclopentyl and cyclohexyl. This definition also applies to cycloalkyl as a part of a composite substituent, for example cycloalkylalkyl etc., unless specifically defined elsewhere.

The term "cycloalkenyl" means alkenyl closed to form a ring including monocyclic, partially unsaturated hydrocarbyl groups. Non-limiting examples include but are not limited to cyclopropenyl, cyclopentenyl and cyclohexenyl. This definition also applies to cycloalkenyl as a part of a composite substituent, for example cycloalkenylalkyl etc., unless specifically defined elsewhere.

The term "cycloalkynyl" means alkynyl closed to form a ring including monocyclic, partially unsaturated groups. Non-limiting examples include but are not limited to cyclopropynyl, cyclopentynyl and cyclohexynyl. This definition also applies to cycloalkynyl as a part of a composite substituent, for example cycloalkynylalkyl etc., unless specifically defined elsewhere.

The term "cycloalkoxy", "cycloalkenyloxy" and the like are defined analogously. Non limiting examples of cycloalkoxy include cyclopropyloxy, cyclopentyloxy and cyclohexyloxy. This definition also applies to cycloalkoxy as a part of a composite substituent, for example cycloalkoxy alkyl etc., unless specifically defined elsewhere.

The term "halogen", either alone or in compound words such as "haloalkyl", includes fluorine, chlorine, bromine or iodine. Further, when used in compound words such as "haloalkyl", said alkyl may be partially or fully substituted with halogen atoms which may be the same or different. Non-limiting examples of "haloalkyl" include chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1-chloroethyl, 1-bromoethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl, l,l-dichloro-2,2,2-trifluoroethyl, and 1,1,1-trifluoroprop-2-yl. This definition also applies to haloalkyl as a part of a composite substituent, for example haloalkylaminoalkyl etc., unless specifically defined elsewhere.

The terms "haloalkenyl", "haloalkynyl" are defined analogously except that, instead of alkyl groups, alkenyl and alkynyl groups are present as a part of the substituent.

The term "haloalkoxy" means straight-chain or branched alkoxy groups where some or all of the hydrogen atoms in these groups may be replaced by halogen atoms as specified above. Non-limiting examples of haloalkoxy include chloromethoxy, bromomethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, dichlorofluoromethoxy, chlorodifluoromethoxy, 1-chloroethoxy, 1-bromoethoxy, 1-fluoroethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2-fluoroethoxy, 2-chloro-2,2-difluoroethoxy, 2,2-dichloro-2-fluoroethoxy, 2,2,2-trichloroethoxy, pentafluoroethoxy and l,l,l-trifluoroprop-2-oxy. This definition also applies to haloalkoxy as a part of a composite substituent, for example haloalkoxyalkyl etc., unless specifically defined elsewhere.

The term "haloalkylthio" means straight-chain or branched alkylthio groups where some or all of the hydrogen atoms in these groups may be replaced by halogen atoms as specified above. Non-limiting examples of haloalkylthio include chloromethylthio, bromomethylthio, dichloromethylthio, trichloromethylthio, fluoromethylthio, difluoromethylthio, trifluoromethy lthio , chlorofluoromethy lthio , dichlorofluoromethy lthio , chlorodifluoromethylthio, 1-chloroethylthio, 1-bromoethy lthio, 1- fluoroethy lthio, 2-fluoroethy lthio, 2,2-difluoroethylthio, 2,2,2-trifluoroethylthio, 2-chloro-2- fluoroethy lthio, 2-chloro-2,2-difluoroethylthio, 2,2-dichloro-2-fluoroethylthio, 2,2,2-trichloroethylthio, pentafluoroethy lthio and l,l,l-trifluoroprop-2-ylthio. This definition also applies to haloalkylthio as a part of a composite substituent, for example haloalkylthioalkyl etc., unless specifically defined elsewhere.

The term "hydroxy" means -OH, Amino means -NRR, wherein R can be H or any possible substituent such as alkyl. Carbonyl means -C(O)-, carbonyloxy means -OC(O)-, sulfinyl means SO, sulfonyl means S(0)2.

The term "alkoxy" used either alone or in compound words included Ci to Cio alkoxy, more preferably Ci to Ce alkoxy. Examples of alkoxy include methoxy, ethoxy, propoxy, 1-methylethoxy, butoxy, 1-methylpropoxy, 2-methylpropoxy, 1,1-dimethylethoxy, pentoxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 2,2-dimethylpropoxy, 1-ethylpropoxy, hexoxy, 1,1-dimethylpropoxy, 1,2-dimethylpropoxy, 1-methylpentoxy, 2-methylpentoxy, 3-methylpentoxy, 4-methylpentoxy, 1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, 2,2-dimethylbutoxy, 2,3-dimethylbutoxy, 3,3-dimethylbutoxy, 1-ethylbutoxy, 2-ethylbutoxy, 1,1,2-trimethylpropoxy, 1,2,2-trimethylpropoxy, 1 -ethyl- 1-methylpropoxy and l-ethyl-2-methylpropoxy and the different isomers. This definition also applies to alkoxy as a part of a composite substituent, for example haloalkoxy, alkynylalkoxy, etc., unless specifically defined elsewhere.

The term "alkylthio" includes branched or straight-chain alkylthio moieties such as methy lthio, ethy lthio, propylthio, 1-methylethy lthio, buty lthio, 1-methylpropylthio, 2-methylpropy lthio, 1,1-dimethylethy lthio, pentylthio, 1 -methy lbuty lthio, 2-methylbutylthio, 3-methylbuty lthio, 2,2-dimethylpropylthio, 1-ethylpropylthio, hexy lthio, 1,1-dimethylpropy lthio, 1,2-dimethylpropylthio, 1 -methy lpenty lthio, 2-methylpenty lthio, 3-methylpenty lthio, 4-methy lpenty lthio, 1,1-dimethy lbuty lthio, 1,2-dimethy lbuty lthio, 1,3-dimethy lbuty lthio, 2,2-dimethylbutylthio, 2,3 -dimethy lbuty lthio, 3,3-dimethylbutylthio, 1- ethylbutylthio, 2-ethylbutylthio, 1,1,2-trimethylpropylthio, 1,2,2-trimethylpropylthio, 1-ethyl-1-methylpropylthio and l-ethyl-2-methylpropylthio and the different isomers.

Halocycloalkyl, halocycloalkenyl, alkylcycloalkyl, cycloalkylalkyl, cycloalkoxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, haloalkylcarbonyl, cycloalkylcarbonyl, haloalkoxylalkyl, and the like, are defined analogously to the above examples.

Non-limiting examples of "alkylsulfinyl" include but are not limited to methylsulphinyl, ethylsulphinyl, propylsulphinyl, 1-methylethylsulphinyl, butylsulphinyl, 1-methylpropylsulphinyl, 2-methylpropylsulphinyl, 1 , 1 -dimethylethylsulphinyl, pentylsulphinyl, 1-methylbutylsulphinyl, 2-methylbutylsulphinyl, 3-methylbutylsulphinyl,

2.2-dimethylpropylsulphinyl, 1-ethylpropylsulphinyl, hexylsulphinyl, 1,1-dimethylpropylsulphinyl, 1,2-dimethylpropylsulphinyl, 1-methylpentylsulphinyl, 2-methylpentylsulphinyl, 3-methylpentylsulphinyl, 4-methylpentylsulphinyl, 1,1-dimethylbutylsulphinyl, 1,2-dimethylbutylsulphinyl, 1,3-dimethylbutylsulphinyl, 2,2-dimethylbutylsulphinyl, 2,3-dimethylbutylsulphinyl, 3,3-dimethylbutylsulphinyl, 1-ethylbutylsulphinyl, 2-ethylbutylsulphinyl, 1,1,2-trimethylpropylsulphinyl, 1,2,2-trimethylpropylsulphinyl, 1 -ethyl- 1-methylpropylsulphinyl and l-ethyl-2-methylpropylsulphinyl and the different isomers. The term "arylsulfinyl" includes Ar-S(O), wherein Ar can be any carbocyle or heterocylcle. This definition also applies to alkylsulphinyl as a part of a composite substituent, for example haloalkylsulphinyl etc., unless specifically defined elsewhere.

Non-limiting examples of "alkylsulfonyl" include but are not limited to methylsulphonyl, ethylsulphonyl, propylsulphonyl, 1-methylethylsulphonyl, butylsulphonyl, 1-methylpropylsulphonyl, 2-methylpropylsulphonyl, 1 , 1 -dimethylethylsulphonyl, pentylsulphonyl, 1-methylbutylsulphonyl, 2-methylbutylsulphonyl, 3-methylbutylsulphonyl,

2.2-dimethylpropylsulphonyl, 1-ethylpropylsulphonyl, hexylsulphonyl, 1,1-dimethylpropylsulphonyl, 1,2-dimethylpropylsulphonyl, 1-methylpentylsulphonyl, 2-methylpentylsulphonyl, 3-methylpentylsulphonyl, 4-methylpentylsulphonyl, 1,1-dimethylbutylsulphonyl, 1,2-dimethylbutylsulphonyl, 1,3-dimethylbutylsulphonyl, 2,2-dimethylbutylsulphonyl, 2,3-dimethylbutylsulphonyl, 3,3-dimethylbutylsulphonyl, 1-ethylbutylsulphonyl, 2-ethylbutylsulphonyl, 1,1,2-trimethylpropylsulphonyl, 1,2,2-trimethylpropylsulphonyl, 1 -ethyl- 1-methylpropylsulphonyl and l-ethyl-2-methylpropylsulphonyl and the different isomers. The term "arylsulfonyl" includes Ar-S(0)2, wherein Ar can be any carbocyle or heterocylcle. This definition also applies to

alkylsulphonyl as a part of a composite substituent, for example alkylsulphonylalkyl etc., unless defined elsewhere.

"Alkylamino", " dialky lamino", and the like, are defined analogously to the above examples.

The term “bicyclic ring or ring system” denotes a ring system consisting of two or more common atom.

The term “aromatic” indicates that the Hueckel rule is satisfied and the term “non-aromatic” indicates that the Hueckel rule is not satisfied.

The terms “carbocycle” or “carbocyclic” or “carbocyclyl” include “aromatic carbocyclic ring system” and “nonaromatic carbocylic ring system” or polycyclic or bicyclic (spiro, fused, bridged, nonfused) ring compounds in which the ring may be aromatic or non-aromatic (where aromatic indicates that the Huckel rule is satisfied and non-aromatic indicates that the Huckel rule is not satisfied).

Non limiting examples of non-aromatic carbocyclic ring system are cyclopropyl, cyclobutyl, cyclopentyl, norbornyl and the like. Non limiting examples of aromatic carbocyclic ring system are phenyl, naphthyl and the like.

The term “aryl” as used herein is a group that contains any carbon-based aromatic group including, but not limited to phenyl, naphthalene, biphenyl, anthracene, and the like. The aryl group can be substituted or unsubstituted. In addition, the aryl group can be a single ring structure or comprise multiple ring structures that are either fused ring structures or attached via one or more bridging groups such as a carbon-carbon bond.

The term “aryl” also comprises “aralkyl” refers to aryl hydrocarbon radicals including an alkyl portion as defined above. Examples include benzyl, phenylethyl, and 6-napthylhexyl. As used herein, the term “aralkenyl” refers to aryl hydrocarbon radicals including an alkenyl portion, as defined above, and an aryl portion, as defined above. Examples include styryl, 3-(benzyl) prop-2-enyl, and 6-napthylhex-2-enyl.

The term “hetero” in connection with rings refers to a ring in which at least one ring atom is not carbon and which can contain 1 to 4 heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur, provided that each ring contains no more than 4 nitrogens, no more than 2 oxygens and no more than 2 sulfurs.

The terms “heterocycle” or “heterocyclic” includes “aromatic heterocycle” or “heteroaryl ring system” and “nonaromatic heterocycle ring system” or polycyclic or bicyclic (spiro, fused, bridged, non-fused) ring compounds in which ring may be aromatic or non-aromatic, wherein the heterocycle ring contains at least one heteroatom selected from N, O, S(0)o-2, and or C ring member of the heterocycle may be replaced by C(=0), C(=S), C(=CR*R*) and C=NR*, * indicates integers.

The term “non-aromatic heterocycle” or “non-aromatic heterocyclic” means three- to fifteen-membered, preferably three- to twelve-membered, saturated or partially unsaturated heterocycle containing one to four heteroatoms from the group of oxygen, nitrogen and sulphur: mono, bi- or tricyclic heterocycles which contain, in addition to carbon ring members, one to three nitrogen atoms and/or one oxygen or sulphur atom or one or two oxygen and/or sulphur atoms; if the ring contains more than one oxygen atom, they are not directly adjacent; for example (but not limited to) oxetanyl, oxiranyl, aziridinyl, thietanyl, tetrahydrofuranyl, tetrahydrothienyl, pyrrolidinyl, isoxazolidinyl, isothiazolidinyl, pyrazolidinyl, oxazolidinyl, thiazolidinyl, imidazolidinyl, 1,2,4-oxadiazolidinyl, 1,2,4-thiadiazolidinyl, 1,2,4-triazolidin-l-yl, l,2,4-triazolidin-3-yl, 1,2,3-triazolidinyl, 1,3,4-oxadiazolidinyl, 1,3,4-thiadiazolidinyl, 1,3,4-triazolidinyl, dihydrofuryl, dihydrothienyl, pyrrolinyl, isoxazolinyl, isothiazolinyl, dihydropyrazolyl, dihydrooxazolyl, dihydrothiazolyl,piperidinyl, pyrazynyl, morpholinyl, thiomorphlinyl, l,3-dioxan-5-yl, tetrahydropyranyl, tetrahydrothienyl, hexahydropyridazinyl, hexahydropyrimidinyl, piperazinyl and cycloserines. This definition also applies to heterocyclyl as a part of a composite substituent, for example heterocyclylalkyl etc., unless specifically defined elsewhere. This definition also applies to heterocyclyl as a part of a composite substituent, for example heterocyclylalkyl etc., unless specifically defined elsewhere.

The term “heteroaryl” or “aromatic heterocyclic” means 5 or 6-membered, fully unsaturated monocyclic ring system containing one to four heteroatoms from the group of oxygen, nitrogen and sulphur; if the ring contains more than one oxygen atom, they are not directly adjacent; 5-membered heteroaryl containing one to four nitrogen atoms or one to three nitrogen atoms and one sulphur or oxygen atom: 5-membered heteroaryl groups which, in addition to carbon atoms, may contain one to four nitrogen atoms or one to three nitrogen atoms and one sulphur or oxygen atom as ring members, for example (but not limited thereto) furyl, thienyl, pyrrolyl, isoxazolyl, isothiazolyl, pyrazolyl, oxazolyl, thiazolyl, imidazolyl, 1,2,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,2,4-triazolyl, 1,3,4-oxadiazolyl, 1,3,4-thiadiazolyl, 1,3,4- triazolyl, tetrazolyl; nitrogen-bonded 5-membered heteroaryl containing one to four nitrogen atoms, or benzofused nitrogen-bonded 5-membered heteroaryl containing one to three nitrogen atoms: 5-membered heteroaryl groups which, in addition to carbon atoms, may contain one to four nitrogen atoms or one to three nitrogen atoms as ring members and in which two adjacent carbon ring members or one nitrogen and one adjacent carbon ring member may be bridged by a buta-1, 3 -diene-1, 4-diyl group in which one or two carbon atoms may be replaced by nitrogen atoms, where these rings are attached to the skeleton via one of the nitrogen ring members, for example (but not limited to) 1-pyrrolyl, 1-pyrazolyl, 1,2,4-triazol-1- yl, 1-imidazolyl, 1,2,3-triazol-l-yl and 1,3,4-triazol-l-yl.

6-membered heteroaryl which contains one to four nitrogen atoms: 6-membered heteroaryl groups which, in addition to carbon atoms, may contain, respectively, one to three and one to four nitrogen atoms as ring members, for example (but not limited thereto) pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, l,3,5-triazin-2-yl, l,2,4-triazin-3-yl and l,2,4,5-tetrazin-3-yl; benzofused 5-membered heteroaryl containing one to three nitrogen atoms or one nitrogen atom and one oxygen or sulphur atom: for example (but not limited to) indolyl, benzimidazolyl, indazolyl, benzofuranyl, benzothiophenyl, benzothiazolyl, and benzoxazolyl; benzofused 6-membered heteroaryl which contains one to three nitrogen atoms: for example (but not limited to) quinolinyl, isoquinolinyl, quinoxalinyl, phthalazinyl, quinazolinyl and cinnolinyl.This definition also applies to heteroaryl as a part of a composite substituent, for example heteroarylalkyl etc., unless specifically defined elsewhere.

Bicyclic 5-6 heteroaryl systems with One bridgehead (Ring Junction) nitrogen atom containing one to three nitrogen atoms or one nitrogen atom and one oxygen or sulphur atom: for example (but not limited to) imidazo[l,2-a]pyridine, imidazo[l,2-a]pyrimidine, [l,2,4]triazolo[l,5-a]pyrimidine, [l,2,4]triazolo[l,5-b]pyridazine, [l,2,4]triazolo[l,5-ajpyrazinc, [l,2,4]triazolo[l,5-a]pyridine, imidazo[l,2-c]pyrimidine, imidazo[l,2-bjpyridazine, [l,2,4]triazolo[l,5-c]pyrimidine, 1 -methyl- lH-indole, imidazo[l,2-a]pyrazine, pyrazolo[l,5-a]pyridine and [l,2,4]triazolo[4,3-a]pyridine.

Non-limiting examples of fused 6-5-membered heteroaryl include Indolizinyl; pyrazolo[l,5-ajpyridinyl; imidazo[l,2-a]pyridinyl; pyrrolo[l,2-a]pyrimidinyl; pyrazolo[l,5-a]pyrimidinyl; imidazo[l,2-a]pyrimidinyl; pyrrolo[l,2-a]pyrazinyl; pyrazolo[l,5-a]pyrazinyl; imidazo[l,2-ajpyrazinyl and the like.

The “alkyl” also comprises “cyclic alkyl” or “cycloalkyl” which means alkyl closed to form a ring. Non limiting examples include but are not limited to cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. This definition also applies to cycloalkyl as a part of a composite substituent, for example cycloalkylalkyl etc., unless specifically defined elsewhere.

The “alkenyl” also comprises “cycloalkenyl” which means alkenyl closed to form a ring including monocyclic, partially unsaturated hydrocarbyl groups. Non limiting examples include but are not limited to cyclopentenyl and cyclohexenyl. This definition also applies to cycloalkenyl as a part of a composite substituent, for example cycloalkenylalkyl etc., unless specifically defined elsewhere.

The “alkynyl” also comprises “cycloalkynyl” which means alkynyl closed to form a ring including monocyclic, partially unsaturated groups. This definition also applies to cycloalkynyl as a part of a composite substituent, for example cycloalkynylalkyl etc., unless specifically defined elsewhere.

The “alkoxy” also comprises “cycloalkoxy”, “cycloalkenyloxy” and the like are defined analogously. Non limiting examples of cycloalkoxy include cyclopropyloxy, cyclopentyloxy and cyclohexyloxy. This definition also applies to cycloalkoxy as a part of a composite substituent, for example cycloalkoxy alkyl etc., unless specifically defined elsewhere.

This definition also applies to heteroaryl as a part of a composite substituent, for example heteroarylalkyl etc., unless specifically defined elsewhere.

Any of the compounds according to the invention can also exist in one or more geometric isomer forms depending on the number of double bonds, chiral center or geometric rearrangement in the compound. The invention thus relates equally to all geometric isomers and to all possible mixtures, in all proportions. The geometric isomers can be separated according to general methods, which are known per se by a person ordinary skilled in the art. Accordingly, the present invention relates to an improved process for the preparation of compound (I) or a salt thereof represented by the formula;

Formula (I)

wherein,

R2 is selected from the group consisting of -NFh, -NH-RZ, -CH2NH2 and -CFh-NH- Rz;

R3, R4 and R5 are independently selected from the group consisting of hydrogen, Ci- Cio-alkyl, C2-Cio-alkenyl, C2-Cio-alkynyl, -C(=0)(0)o-iRx and C3-Cio-cabocylyl; or

R3 and R4 or R3 and R5 or R4 and R5 together with the atom they are attached form C3- Cio-carbocyclic/heterocyclic ring wherein R3, R4, R5 and said ring may substituted with one or more R groups;

R is selected from the group consisting of hydrogen, halogen, Ci-C6-alkyl, C2-C6- alkenyl, C2-C6-alkynyl, Ci-C6-alkoxy, Ci-C6-haloalkoxy, Ci-C6-alkylthio, C1-C6- haloalkylthio, -COOH, -ester, -C(=O)(O)0-iRx, ORy, -SH, -CN, -NH2, -NH(CI-C6- alkyl), -N(Ci-C6-alkyl)2 and -NH-S02-Rz;

Rx is selected from the group consisting of hydrogen, Ci-C6-alkyl, C1-C6- haloalkyl and aryl;

Ry is selected from the group consisting of hydrogen, Ci-C6-alkyl, C1-C6- haloalkyl, -C(=0)(0)o-iRx and aryl;

Rz is selected from the group consisting of hydrogen, Ci-C6-alkyl, C1-C6- haloalkyl, ORy, -C(=0)(0)o-iRx and aryl;

comprising the step of hydrogenation of compound of formula (II) represented by the formula,

Formula(II)

wherein,

R1 is a reducible functional group selected from the group consisting of -NO2, -CN, - CH=N-RZ and =N-RZ; provided when R1 represent =N-RZ then, one of the group from R3, R4 or R5 is absent;

R3, R4, R5 and Rz are same as defined above;

in the presence of a transition metal complex catalyst represented by the formula (Z), and a hydrogen source

(M)n (X)n (A)n

(Z)

wherein M is a transition metal selected from Palladium (Pd), Platinum (Pt), Nickel (Ni), Copper (Cu), Cobalt (Co), Manganese (Mn), Vanadium (V), Zinc (Zn), Chromium (Cr), Cadmium (Cd), Rubidium (Rb), Lanthanum (La), Lead (Pb), Zirconium (Zr), Gold (Au), Mercury (Hg), Scandium (Sc) and Titanium (Ti),

X is a halogen selected from fluorine (F), chlorine (Cl), bromine (Br) and iodine (I), n= 1-10,

A is an organic moiety selected from substituted or unsubstituted alkyl, alkenyl, alkynyl, carbocycle, heterocycle, aryl, heteroaryl, mono or bicyclic aromatic, mono or bicyclic heteroaromatic, saccharin, saccharin derivatives.

In the context of the present invention, the term “hydrogenation” when used in reference to any element; including a process step e.g. hydrogenation of compound (II); it is intended to mean that the reducible functional group of compound (II) is subject to treat with an hydrogen source, to obtain hydrogenated product.

In an embodiment, the hydrogen source used for the hydrogenation reaction is hydrogen gas.

In an embodiment, the present invention relates to the use of palladium complex compound (Z1) as catalyst for hydrogenation reaction:

(Pd)n (X)n(A)n

(Z1)

wherein X is a halogen selected from fluorine (F), chlorine (Cl), bromine (Br) and iodine (I), n= 1-10,

A is an organic moiety selected from substituted or unsubstituted alkyl, alkenyl, alkynyl, carbocycle, heterocycle, aryl, heteroaryl, mono or bicyclic aromatic, mono or bicyclic heteroaromatic, saccharin, saccharin derivatives.

In yet another embodiment, the present invention relates to the use of a palladium complex compound (Z2) as catalyst for hydrogenation reaction:

(Pd)n (X)n (Saccharin)n

(Z2)

wherein X is a halogen selected from fluorine (F), chlorine (Cl), bromine (Br) and iodine (I), n= 1-10.

In a specific embodiment, the transition metal complex is palladium (Pd)-saccharin complex compound (Z3) and it is further used as catalyst for hydrogenation reaction:

Pd (Cl)2 (Saccharin)2

(Z3)

Accordingly, in an embodiment the present invention relates to a process for the preparation of compound of formula (I) or a salt thereof;

Formula(I)

wherein,

R2 is selected from the group consisting of -Nth, -NH-RZ, -CH2NH2 and -Cth-NH- Rz;

R3, R4 and R5 are independently selected from the group consisting of hydrogen, Ci- Cio-alkyl, C2-Cio-alkenyl, C2-Cio-alkynyl, -C(=0)(0)o-iRx and C3-Cio-cabocylyl; or

R3 and R4 or R3 and R5 or R4 and R5 together with the atom they are attached form C3- Cio-carbocyclic/heterocyclic ring wherein R3, R4, R5 and said ring may substituted with one or more R groups;

R is selected from the group consisting of hydrogen, halogen, Ci-C6-alkyl, C2-C6- alkenyl, C2-C6-alkynyl, Ci-C6-alkoxy, Ci-C6-haloalkoxy, Ci-C6-alkylthio, C1-C6- haloalkylthio, -COOH, -ester, -C(=O)(O)0-iRx, ORy, -SH, -CN, -Nth, -NH(CI-C6- alkyl), -N(Ci-C6-alkyl)2 and -NH-S02-Rz;

Rx is selected from the group consisting of hydrogen, Ci-C6-alkyl, C1-C6- haloalkyl and aryl;

Ry is selected from the group consisting of hydrogen, Ci-C6-alkyl, C1-C6- haloalkyl, -C(=0)(0)o-iRx and aryl;

Rz is selected from the group consisting of hydrogen, Ci-C6-alkyl, C1-C6- haloalkyl, ORy, -C(=0)(0)o-iRx and aryl;

comprising the step of hydrogenation of compound of formula (II),

Formula(II)

wherein,

R1 is a reducible functional group selected from the group consisting of -NO2, -CN, - CH=N-RZ and =N-RZ; provided when R1 represent =N-RZ then, one of the group from R3, R4 or R5 is absent;

and R3, R4, R5 and Rz are same as defined above;

in the presence of palladium (Pd) -saccharin complex catalyst (Z3) represented by the formula, and a hydrogen source;

Pd (Cl)2 (Saccharin)2

(Z3)

Another embodiment the present invention relates to a process for the preparation of compound of formula (I A) or a salt thereof;

wherein, R2 is selected from the group consisting of -Nth, -CH2NH2 and -Cth-NH-Rz;

R is selected from the group consisting of hydrogen, halogen, Ci-C6-alkyl, C2-C6- alkenyl, C2-C6-alkynyl, Ci-C6-alkoxy, Ci-C6-haloalkoxy, Ci-C6-alkylthio, C1-C6- haloalkylthio, -COOH, -ester, -C(=O)(O)0-iRx, ORy, -SH, -CN, -NH2, -NH(CI-C6- alkyl), -N(Ci-C6-alkyl)2 and -NH-S02-Rz,

m = 0-5,

comprising the step of hydrogenation of compound of formula (IIA),

wherein, R1 is a reducible functional group selected from the group consisting of - NO2, -CN and -CH=N-RZ; R, Rx,Ry andRz are same as defined above;

in the presence of palladium (Pd) -saccharin complex catalyst (Z3) represented by the formula, and a hydrogen source

Pd (Cl)2 (Saccharin)2

(Z3)

In a specific embodiment, the process for the preparation of compound (I) or a salt thereof; comprises the steps of:

(i) suspending palladium chloride (PdCh) and lithium chloride in a solvent;

(ii) stirring the reaction mixture of step (i);

(iii) adding saccharin to the solution of step (ii) and continue stirring;

(iv) optionally, isolating the palladium (Pd) -saccharin complex compound (Z3);

(v) adding substrate compound (II) to the solution containing palladium (Pd) -saccharin complex catalyst (Z3) in a solvent;

(vi) applying the hydrogen source to the stirring reaction mixture of step (v);

(vii) optionally, applying pressure conditions;

(viii) optionally, heating the reaction mixture of step (vii);

(ix) isolating the desired product.

The process of the present invention as per the specific embodiment described above is illustrated in the following Scheme-2,

Hydrogen Source

(HA) (IA)

Scheme-2

wherein, Ri, R, R2 and n as defined in the specification.

The solvent used in the step-(i) to step-(ix) of the above process (as depicted in the Scheme-2) is selected from halogenated solvents such as dichloromethane, 4-bromotoluene, diiodomethane, carbon tetrachloride, chlorobenzene and chloroform; alcoholic solvent such as methanol, ethanol, isopropanol, t-amyl alcohol, t-butyl alcohol and hexanol; an ether solvent such as tetrahydrofuran, cyclopentyl methyl ether, 2-methyltetrahydrofuran, diethyl ether and 1,4-dioxane; a ketone selected from methyl ethyl ketone, acetone; an aprotic solvent such as acetonitrile, /V,/V-dimethyl formamide (DMF), /V,/V-dimethyl acetamide, dimethyl sulfoxide (DMSO) and N- m c t h y lpy rro 1 i do n c (NMP); an aromatic solvent such as toluene, xylene and benzene; acetone; water or a mixture thereof, and other polar as well as non-polar solvents.

In the context of the present invention, the term “optionally” when used in reference to any element; including a process step e.g. isolation of catalyst; it is intended to mean that the subject element is isolated, or alternatively, is not isolated from the reaction mixture and directly used for the further chemical reaction. Both alternatives are intended to be within the scope of the present invention

In an embodiment, the transition metal complex catalyst is optionally isolated during the reaction and substrate transformation.

In the context of the present invention, the term “optionally” when used in reference to any element; including a process step e.g. applying pressure; it is intended to mean that the reaction is performed in added pressure conditions, or alternatively, the reaction is performed at atmospheric pressure without applying any added pressure on reaction. Both alternatives are intended to be within the scope of the present invention

The term ‘applying pressure conditions’ referred to in the step (vii) of the above process (as depicted in the Scheme-2) is intended to mean that the reaction is performed at pressure ranging from atmospheric pressure to the applied pressure conditions up to 25 Kg/cm2.

In the context of the present invention, the term “optionally” when used in reference to any element; including a process step e.g. heating the reaction mixture; it is intended to mean that the reaction is performed at room temperature, or alternatively, the reaction is performed at elevated temperature up to the reflux temperature of the solvent. Both alternatives are intended to be within the scope of the present invention

The term ‘heating the reaction mixture’ referred to in the step (vii) of the above process (as depicted in the Scheme-2) is intended to mean that the reaction temperature can be increased from 30°C to the reflux temperature of the solvent.

In an embodiment the ‘hydrogen source’ used in the step (vi) of the above process (as depicted in the Scheme-2) corresponds to hydrogen gas.

The term ‘isolating the desired product’ referred to in the step (ix) of the above process (as depicted in the Scheme-2) corresponds to the any of the steps involving biphasic separation, separation of organic phase, filtration, evaporation of solvent, cooling, precipitation, washing and drying.

The overall process of the present invention involving preparation of a specific substrate compound (IA) through hydrogenation is illustrated in the following Scheme-3:

Scheme-3 (I )

The process illustrated in the above scheme-3 comprises, dissolving the compound (IIA) in a solvent such as methanol, treatment of the compound (IIA) with hydrogen gas in presence of palladium (Pd) -saccharin complex (Z3) under atmospheric pressure. The reaction mass was filtered off and the filtrate was concentrated. The residue was treated with water and the resulted solid was filtered off to get the desired product with yield of 85% and purity of > 99% (HPLC).

It is evident from the processes reported in the prior art that the routinely implemented catalytic hydrogenation method such as using Pd/C, requires an autoclave with applied reaction pressure of about 500 psi (about 35 kg/cm2); whereas the process of the present invention is performed at atmospheric pressure and provides the pure desired product, the

compound-IA in a yield of 85% and purity of > 99% (HPLC). This amounts to a significant advantage over the processes reported in the prior art in terms of handling and instrument requirements.

In yet another embodiment, the present invention relates to an improved process for the preparation of compound (I) (as described herein) or a salt thereof; comprising the steps of

(1) reacting palladium chloride with saccharin to form the palladium-saccharin complex catalyst (Z3);

(2) optionally, isolating the palladium- saccharin complex;

(3) treating the compound (II) (as described herein) with a hydrogen source in the presence of the palladium- saccharin complex obtained from step (2).

In an embodiment the transition metal complex (Z) is immobilized.

In the context of the present invention, the term “immobilized”, when used in reference to any element; including a process step or a product e.g. immobilized transition metal complex (Z); is intended to mean the immobilization of the transition metal complex (Z) on an appropriate inert support material. The method of formation of immobilized catalyst may comprises grafting, physical adsorption, ion-pair formation, and entrapment.

In yet another embodiment, the present invention relates to the use of immobilized transition metal complex (Z) as a catalyst for hydrogenation reactions; wherein the immobilized catalyst is repeatedly used for hydrogenation reactions without any activation.

In an embodiment, the present invention relates to the use of immobilized transition metal complex (Z) as a catalyst for hydrogenation reactions in a continuous -flow system; wherein the immobilized catalyst is repeatedly used for hydrogenation reactions without any activation.

In one embodiment the amount of the catalyst (Z) used is in the range of 0.02 to 0.4 mol % of the compound of formula (I), preferably the amount of the catalyst used is in the range of 0.04 to 0.2 mol % of the compound of formula (I),

In specific embodiment the amount of the catalyst (Z3) used is in the range of 0.02 to 0.4 mol % of the compound of formula (I), preferably the amount of the catalyst used is in the range of 0.04 to 0.2 mol % of the compound of formula (I),

The foregoing definitions provided herein for the terminologies used in the present disclosure are for illustrative purpose only and in no manner limit the scope of the present invention disclosed in the present disclosure.

As used herein, the terms "comprises", "comprising", "includes", "including", “consisting” or any other variation thereof, are intended to cover a non-exclusive inclusion, subject to any limitation explicitly indicated. For example, a process or method that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such process or method.

Also, the indefinite articles "a" and "an" preceding an element or component of the present invention are intended to be nonrestrictive regarding the number of instances (i.e. occurrences) of the element or component. Therefore "a" or "an" should be read to include one or at least one, and the singular word form of the element or component also includes the plural unless the number is obviously meant to be singular.

The specification herein and the various features and advantageous details thereof are explained with reference to the non-limiting examples in the description. Descriptions of well-known components and processing techniques are omitted so as to not unnecessarily obscure the embodiments herein. The examples used herein are intended merely to facilitate an understanding of ways in which the specification herein may be practiced and to further enable those of skilled in the art to practice the specification herein. Accordingly, the examples should not be construed as limiting the scope of the specification herein.

Any discussion of documents, acts, materials, devices, articles and the like that has been included in this specification is solely for the purpose of providing a context for the disclosure. It is not to be taken as an admission that any or all of these matters form a part of the prior art base or were common general knowledge in the field relevant to the disclosure as it existed anywhere before the priority date of this application.

The numerical values mentioned in the description and the foregoing claims though might form a critical part of the present invention of the present disclosure, any deviation from such numerical values shall still fall within the scope of the present disclosure if that deviation follows the same scientific principle as that of the present invention disclosed in the present disclosure.

The invention is further illustrated by the following examples which are provided to be exemplary of the invention, and do not limit the scope of the invention. While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.

Examples:

Example 1: Preparation of palladium (Pd)-saccharin complex (Z3):

Pd (Cl)2 (Saccharin)2

(Z3)

Palladium chloride (10 g, 0.056 M) and lithium chloride (5.64 g, 0.13 M) were added to methanol (126 mL). The reaction mixture was stirred for 2 hrs at 25 °C. A solution of saccharin (10.42 g, 0.057 M) and sodium acetate (6.94 g, 0.084 M) in methanol (100 g) was added to the above reaction mixture and stirred further for 8 hrs at 25 °C. The slurry was filtered to obtain desired compound (yield: 85%).

^NMR (400 MHz, DMSO- d6 ): d 7.56-7.76 (m, 8H);

13C NMR (100 MHz, DMSO -d6): 119.2, 120.0, 122.58, 123.09, 131.13, 131.67, 132.48, 132.80, 133.0, 134.73, 142.69, 145.28, 165.46, 168.06.

Example 2: Preparation of 2-amino-3-methyl-benzoic acid (IA):

3-Methyl-2-nitrobenzoic acid (IIA) (8 g, 0.0055M) and the palladium (Pd)- saccharin complex (Z1) (0.05 g) were added to an autoclave, the reaction mixture was stirred for 8 hrs at 25 °C under 20 kg/cm2 of hydrogen gas pressure. The reaction mixture was filtered and the solvent was evaporated under reduced pressure. The residue was suspended in water (32 g) for 1 h to form slurry. The slurry was filtered and dried under reduced pressure to obtain the desired compound IA (yield: 97.3%).

MR (400 MHz, DMSO- 6) d 2.08 (s, 3H), d 6.43-6.46 (t, 1H), d 7.13-7.14 (d, 1H), d
7.60 (d, 1H);

13C NMR (100 MHz, DMSO -d6) 17.61, 109.48, 114.42, 123.08, 129.15, 134.52, 149.48, 170.19. MS m/z 152.03 [M+H]+.

Example 3: Preparation of methyl 2-amino-4-(aminomethyl)benzoate (IB):

( )

Methyl-4-cyano-2-nitrobenzoate (IIB) (2 g, 0.0097M) and the palladium (Pd) -saccharin complex (Z1) (0.2 g) were added to an autoclave, the reaction mixture was stirred for 8 hrs at 25 °C under 20 kg/cm2 of hydrogen gas pressure. The reaction mixture was filtered and the solvent was evaporated under reduced pressure to obtain the desired compound IB (yield: 85%).

Example 4: Preparation of diethyl aminomalonate

A solution of diethyl hydroxyiminomalonate (10.2 g, 0.054 mol) in methanol (40 g) was prepared palladium (Pd) -saccharin complex (Z*)(2 g) was added to the above solution and maintained 8 kg/cm2 hydrogen gas in an autoclave for 5 h at 25 °C. After completion of the reaction, the catalyst was filtered, followed by evaporation of the solvent under reduced pressure to obtain diethyl aminomalonate (8.35 g, 90.5% yield).

1.23 (t, 6H), d 4.24-4.28 (m, 4H), d 5.03 (s, 1H), d 9.18 (bs, 2H);

13C NMR (100 MHz, DMSO-dd), 13.81, 54.75, 62.84, 163.81. MS m/z 152.03 [M+H]+.

we claim

1. A process for the preparation of compound of formula (I) or a salt thereof;

Formula (I)

wherein, R2 is selected from the group consisting of -NFb, -NH-RZ, -CH2NH2, -CH2- NH-RZ;

R3, R4 and R5 are independently selected from the group consisting of hydrogen, Ci- Cio-alkyl, C2-Cio-alkenyl, C2-Cio-alkynyl, -C(=0)(0)o-iRx, C3-Cio-cabocylyl;

or

R3 and R4 or R3 and R5 or R4 and R5 together with the atom they are attached form C3- Cio-carbocyclic/heterocyclic ring wherein R3, R4, R5 and said ring may substituted with one or more R groups;

R is selected from the group consisting of hydrogen, halogen, Ci-C6-alkyl, C2-C6- alkenyl, C2-C6-alkynyl, Ci-C6-alkoxy, Ci-C6-haloalkoxy, Ci-C6-alkylthio, C1-C6- haloalkylthio, -COOH, -ester, -C(=O)(O)0-iRx, ORy, -SH, -CN, -NH2, -NH(CI-C6- alkyl), -N(Ci-C6-alkyl)2, -NH-S02-Rz;

Rx is selected from the group consisting of hydrogen, Ci-C6-alkyl, C1-C6- haloalkyl and aryl;

Ry is selected from the group consisting of hydrogen, Ci-C6-alkyl, C1-C6- haloalkyl, -C(=0)(0)o-iRx and aryl;

Rz is selected from the group consisting of hydrogen, Ci-C6-alkyl, C1-C6- haloalkyl, ORy, -C(=0)(0)o-iRx and aryl;

comprising the step of hydrogenation of compound (II) represented by the formula,

Formula(II)

wherein, R1 is a reducible functional group selected from the group consisting of - NO2, -CN, -CH=N-RZ and =N-RZ ; provided when R1 represent =N-RZ then, one of the group from R3, R4 or R5 is absent; R3, R4 and R5 are same as defined above;

in the presence of palladium (Pd) -saccharin complex catalyst, compound of formula (Z3), and a hydrogen source,

Pd (Cl)2 (Saccharin)2

(Z3)

2. The process for the preparation of compound of formula (I) as claimed in claim 1, wherein compound of formula (I) is (IA) or a salt thereof;

wherein, R2 is selected from the group consisting of -Nth, -CH2NH2, -Cth-NH-Rz;

R is selected from the group consisting of hydrogen, halogen, Ci-C6-alkyl, C2-C6- alkenyl, C2-C6-alkynyl, Ci-C6-alkoxy, Ci-C6-haloalkoxy, Ci-C6-alkylthio, C1-C6- haloalkylthio, -COOH, -ester, -C(=O)(O)0-iRx, ORy, -SH, -CN, -Nth, -NH(CI-C6- alkyl), -N(Ci-C6-alkyl)2, -NH-S02-Rz;

m = 0-5,

comprising the step of hydrogenation of compound of formula (IIA),

wherein, R1 is a reducible functional group selected from the group consisting of - NO2, -CN, -CH=N-RZ; R, Rx Ry andRz are same as defined above;

in the presence of palladium (Pd) -saccharin complex catalyst, compound of formula (Z3), and a hydrogen source;

Pd (Cl)2 (Saccharin)2

(Z3)

The process for the preparation of compound of formula (I) as claimed in claim 1, wherein said process comprising the steps of:

(i) suspending palladium chloride (PdCh) and lithium chloride in a suitable solvent;

(ii) stirring the reaction mixture of step (i);

(iii) adding saccharin to the solution of step (ii) and continue stirring;

(iv) optionally, isolating the palladium (Pd) -saccharin complex compound (Z3);

(v) adding substrate compound of formula (II) to the solution containing palladium (Pd) -saccharin complex catalyst (Z3) in a suitable solvent;

(vi) applying the hydrogen source to the stirring reaction mixture of step (v);

(vii) optionally, applying pressure conditions;

(viii) optionally, heating the reaction mixture of step (vii);

(ix) isolating the desired product.

4. The process for the preparation of compound of formula (I) as claimed in claim 1, wherein said process comprising the steps of:

(1) reacting palladium chloride with saccharin to form the palladium-saccharin complex catalyst (Z3);

(2) optionally, isolating the palladium- saccharin complex;

(3) treating the compound of formula (II) with a suitable hydrogen source in the presence of the palladium- saccharin complex obtained from step (2).

5. The process as claimed in any one of claims 1 to 3, wherein the amount of the catalyst used is in the range of 0.02 to 0.4 mol % of the compound of formula (I).

6. The process for the preparation of compound of formula (I) as claimed in claim 1;

wherein said suitable solvent is selected from the group consisting of protic solvents, polar aprotic solvents and nonpolar solvents, including aromatic hydrocarbons, chlorinated hydrocarbons, ethers, aliphatic hydrocarbons, alcohols, esters, ketones, amides, water or mixtures thereof.

7. The process for the preparation of compound of formula (I) as claimed in claim 1 or 2;

wherein R2 is -Nth and R is selected from the group consisting of halogen, C1-C6- alkyl, -COOH, -COORx, -CN, -Nth, -NH(Ci-C6-alkyl), -N(Ci-C6-alkyl)2, -NH-SO2- Rx.

8. The process for the preparation of compound of formula (IA) as claimed in claim 2;

wherein m is selected from 1 to 3.

9. The process for the preparation of compound of formula (I) as claimed in claim 1;

wherein said compound of formula (I) is selected from 2-amino-3-methyl-benzoic acid, methyl 2-amino-4-(aminomethyl)benzoate or diethyl aminomalonate.

10. The process for the preparation of compound of formula (I) as claimed in claim 1;

wherein said compound of formula (II) is selected from Methyl-4-cyano-2- nitrobenzoate, 3-Methyl-2-nitrobenzoic acid or diethyl hydroxyiminomalonate.

11. A transition metal complex (Z) for catalyzing the hydrogenation reactions:

(M)n (X)n (A)n

(Z)

wherein M is a transition metal selected from Palladium (Pd), Platinum (Pt), Nickel (Ni), Copper (Cu), Cobalt (Co), Manganese (Mn), Vanadium (V), Zinc (Zn), Chromium (Cr), Cadmium (Cd), Rubidium (Rb), Lanthanum (La), Lead (Pb), Zirconium (Zr), Gold (Au), Mercury (Hg), Scandium (Sc) and Titanium (Ti),

X is a halogen selected from fluorine (F), chlorine (Cl), bromine (Br) and iodine (I), n= 1-10,

A is an organic moiety selected from substituted or unsubstituted alkyl, alkenyl, alkynyl, carbocycle, heterocycle, aryl, heteroaryl, mono or bicyclic aromatic, mono or bicyclic heteroaromatic, saccharin, saccharin derivatives.

12. The transition metal complex as claimed in claim 11, wherein said complex represent as palladium complex compound (Z1):

(Pd)n (X)n(A)n

(Z1)

wherein X is a halogen selected from fluorine (F), chlorine (Cl), bromine (Br) and iodine (I),

n= 1-10,

A is an organic moiety selected from substituted or unsubstituted alkyl, alkenyl, alkynyl, carbocycle, heterocycle, aryl, heteroaryl, mono or bicyclic aromatic, mono or bicyclic heteroaromatic, saccharin, saccharin derivatives.

13. The transition metal complex as claimed in claim 11, wherein said complex represented as (Pd)-saccharin complex compound (Z3):

Pd (Cl)2 (Saccharin)2

(Z3)

wherein said transition metal complex (Z3) catalyses hydrogenation reactions.