1012065-72-3Relevant articles and documents
An efficient process for the manufacture of carmegliptin
Abrecht, Stefan,Adam, Jean-Michel,Bromberger, Ulrike,Diodone, Ralph,Fettes, Alec,Fischer, Rolf,Goeckel, Volker,Hildbrand, Stefan,Moine, Gerard,Weber, Martin
, p. 503 - 514 (2012/01/03)
A short and high-yielding synthesis of carmegliptin (1) suitable for large-scale production is reported. The tricyclic core was assembled efficiently by a decarboxylative Mannich addition-Mannich cyclization sequence. Subsequent crystallization-induced dynamic resolution of enamine 7 using (S,S)-dibenzoyltartaric acid was followed by diastereoselective enamine reduction to give the fully functionalized tricyclic core with its three stereogenic centers. The C-3 nitrogen was introduced by Hofmann rearrangement of amide 28, and the resulting amine 10 was coupled with (S)-fluoromethyl lactone 31. Following cyclization to lactam 13 and amine deprotection, 1 was obtained in 27-31% overall yield with six isolated intermediates.
PROCESS FOR THE PREPARATION OF PYRIDO [2,1-a] ISOQUINOLINE DERIVATIVES COMPRISING OPTICAL RESOLUTION OF AN ENAMINE
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Page/Page column 10, (2008/06/13)
This invention relates to a process for the preparation of pyrido[2,1-a]isoquinoline derivatives of the formula wherein R1, R2, R3 and R4 are defined in the specification, comprising the optical resolution of an