- EXPEDIENT SYNTHESIS OF SITAGLIPTIN
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Novel intermediates are disclosed as intermediates for preparation of a Sitagliptin. A novel synthetic method to prepare Sitagliptin using the said intermediates is also disclosed.
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Paragraph 00371; 00372
(2015/09/23)
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- PROCESS FOR PREPARATION OF (2R)-4-OXO-4-[3- (TRIFLUOROMETHYL)-5,6-DIHYDRO [1,2,4]-TRIAZOLO[4,3-A]PYRAZIN- 7(8H)-YL]-L-(2,4,5-TRIFLUOROPHENYL)BUTAN-2-AMINE and NEW IMPURITIES IN PREPARATION THEREOF
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The present invention relates to synthesis of β-amino acid derivatives of formula (I) and its salts of formula (Ia) by a novel process. The process comprises the reduction of a protected or unprotected prochiral β-amino acrylic acid or derivative there of, by using borane containing reducing agents at atmospheric pressure. The resulting racemic β-amino compound is resolved to a pure stereoisomer of formula (I), specifically to (2R)-4-oxo-4-[3-Ctrifluoromethyl)-5,6-dihydrol[1,2,4]triazolo[4,3-alpyrazin-7(8H)-yl]-1-(2,4,4-trifluorophenyl)butan-2-amine. In an embodiment the invention disclosed polymorphic forms of formula (I), phosphate salt of formula (I) and also a Dibenzoyl-L-tartaric acid salt of formula (I).
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- PROCESS FOR THE PREPARATION OF SITAGLIPTIN AND ITS INTERMEDIATES
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The present invention relates to novel and improved processes for the preparation of Sitagliptin compound of formula (1) and its intermediates.
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Page/Page column 52-53
(2010/11/05)
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- IMPROVED PROCESS FOR PREPARATION OF (2R)-4-OXO-4-[3- (TRIFLUOROMETHYL)-5,6-DIHYDRO [1,2,4]-TRIAZOLO[4,3-A]PYRAZIN- 7(8H)-YL]-L-(2,4,5-TRIFLUOROPHENYL)BUTAN-2-AMINE and NEW IMPURITIES IN PREPARATION THEREOF
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The present invention relates to synthesis of β-amino acid derivatives of formula (I) and its salts of formula (Ia) by a novel process. The process comprises the reduction of a protected or unprotected prochiral β-amino acrylic acid or derivative there of, by using borane containing reducing agents at atmospheric pressure. The resulting racemic β-amino compound is resolved to a pure stereoisomer of formula (I), specifically to (2R)-4-oxo-4- [3-Ctrifluoromethyl)-5, 6-dihydrol [1,2,4]triazolo [4,3-alpyrazin-7(8H)-yl]-1-(2,4,4-trifluorophenyl)butan-2-amine. In an embodiment the invention disclosed polymorphic forms of formula (I), phosphate salt of formula (I) and also a Dibenzoyl-L-tartaric acid salt of formula (I).
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Page/Page column 61
(2010/04/25)
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- Direct asymmetric reductive amination
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(Chemical Equation Presented) Asymmetric reductive amination of β-keto amides catalyzed by the chiral catalyst Ru(OAc)2 ((R)-dm-segphos) produces unprotected β-amino amides with high yields and high enantioselectivities (94.7-99.5% ee). This "one-pot" methodology is general in substrate scope and has been successfully employed to produce sitagliptin with 99.5% ee and 91% assay yield. The excellent reaction efficiency is attributed to the remarkable tolerance to high concentrations of ammonium ion, the high chemoselectivity, and the high enantioselectivity (99.5% ee) of the Ru catalyst system.
- Steinhuebel, Dietrich,Sun, Yongkui,Matsumura, Kazuhiko,Sayo, Noboru,Saito, Takao
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supporting information; experimental part
p. 11316 - 11317
(2011/03/19)
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