New Polymorphic Forms Of Sitagliptin Phosphate And Processes Thereof

FIELD OF INVENTION: The present invention discloses four new polymorphic forms of Sitagliptin Phosphate and process thereof. The present invention also discloses novel processes for the preparation of other known polymorphic forms of Sitagliptin phosphate reported in literature. BACKGROUD OF INVENTION: Sitagliptin phosphate having chemical name 7-[(3R)-3-Amino-1-0x0-4-(2,4,5-tri,luorophenyl)butyl]-5,6,7,8-tetrahydro-3-(trifluoromethyl)- 1,2,4-triazolo[4,3-alpyrazine phosphate salt has the following structural formula Sitagliptin is disclosed in WO 031004498 and U.S. Pat. No. 6,699,871. Sitagliptin phosphate salt is disclosed in US patent application 200510032804. Sitagliptin or Sitagliptin phosphate is a dipeptidyl peptidase- IV (DPP-IV) inhibitor and is useful for the treatment and prevention of Type 2 diabetes, hyperglycemia, insulin resistance, obesity, and high blood pressure. Sitagliptin hydrochloride is prepared from 2,4,5-trifluorobenzyl chloride. The major disadvantages of this process are that it involves multi-step synthesis; use of hazardous chemicals such as butyl lithium, diazomethane and silver benzoate; and low overall yield (1 8%). U.S. Patent application 200510032804 discloses a (2R)-4-0x0-4-[3-( trifluoromethy I)-5,6-dihydro [1,2,4]triazolo[4,3-a]pyrazin-7(8H)yl]-l-(2,4,5-trifluorophenyl)butan-2-amine dihydro -- \ t 1 9 Ju#.2m' \ r"48 . I 4 . $0 ?-tr q, i;"! - L 1 ,,-..'- \ n \ < s T CF*; . -" t "fPh-- 'I - -. 4 d gen phosphate monohydrate, also known as Sitagliptin phosphate monohydrate. The commercial I JANUVIA tablets contain Sitagliptin phosphate monohydrate. U.S. Patent application 200610287528 discloses three polymorphic forms (Form I, Form I1 and Foml 111) of anhydrous Sitagliptin phosphate and crystalline solvates of Sitagliptin phosphate (e.g., nthanol solvate). This publication reports that Form I1 is a desolvated anhydrate form, which is metastable and converts into anhydrous forms such as Form I or Form 111 or mixtures thereof in about 2 hours at about 45" C. The ethanol solvate is also not a stable form and can be converted to desolvated Form I1 by (a) drying with nitrogen flow over the sample for about 5 hours at about 25" C. or (b) drying in vacuum for about 5 hours at about 25" C. Upon grinding or compaction of Form I, Form I can be converted into Form 111. However, Form 111 is a stable form at low temperature and is stable below 34' C. U.S. Patent application 200710021430 (or WO 20051030127) discloses an unhydrate polymorph form of Sitagliptin phosphate (Form IV). Form IV is prepared by heating Sitagliptin phosphate monohydrate above 58" C. for about 8 hours. This publication reports that Form IV is also a metastable form and it converts into a crystalline Sitagliptin phosphate monohydrate slowly under ambient conditions and rapidly under high relative humidity (98%) condition at room temperature. U.S. Patent application 20071028194 discloses a composition comprising an amorphous form of Sitagliptin phosphate, which is obtained by freeze-drying of Sitagliptin Phosphate in aqueous solutions. Amorphous Sitagliptin Phosphate is usually less stable, both chemically and physically in comparison to crystalline forms. W020 1000469 discloses crystalline hydrochloride, fumarate, malate, sulfate, phosphate, I succinate, lactate, glycolate, maleate, citrate and mesylate salts of Sitagliptin. W020 100 1278 1 discloses novel crystalline forms of galactarate, hemi-L-malate, D- gluconate, sucinate, hydrobromide, thiocyanate, oxalate, L-asparate, ethanedisulfonate, pyroglutamate, glutarate, acetate forms of Sitagliptin. WIPO patent application W020 1011 3 1035 Sitagliptin dihydrogenphosphate form M, characterized by an XRPD spectrum comprising the following degrees 28 peaks: 5.0, 14.3, 18.6, - -1 p.L *-,"tv / 0 9 JUN 2011 o oF.j b -.. I ,$ , Q - a Ti I-' f 4 . I 3 < ' ,. d . '* 24.0 i 0.2 degrees 28. Preferably Sitagliptin dihydrogkn