반응식
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:14][C:15]1[CH:20]=[C:19]([F:21])[C:18]([F:22])=[CH:17][C:16]=1[F:23])[CH2:10][C:11]([OH:13])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[F:25][C:26]([F:37])([F:36])[C:27]1[N:31]2[CH2:32][CH2:33][NH:34][CH2:35][C:30]2=[N:29][N:28]=1>>[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:14][C:15]1[CH:20]=[C:19]([F:21])[C:18]([F:22])=[CH:17][C:16]=1[F:23])[CH2:10][C:11]([N:34]1[CH2:33][CH2:32][N:31]2[C:27]([C:26]([F:37])([F:25])[F:36])=[N:28][N:29]=[C:30]2[CH2:35]1)=[O:13])=[O:7])([CH3:2])([CH3:3])[CH3:4]참가 물질
실험 절차
(3R)-3-[N-(tert-Butoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoic acid (07) was coupled with 3-trifluoromethyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine hydrochloride (11) to obtain Boc-protected sitagliptin free base, 7-[(3R)-3-[N-(tert-butoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoyl]-3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-a]pyrazine (12). The coupling was preferably carried out by using coupling agents such as EDC-HCl, 1-hydroxybenzotriazole and a suitable base such as N,N-diisopropylethylamine. The coupling was preferably carried out in an aprotic solvent such as N,N-dimethylformamide or N,N-dimethylacetamide at 0-30° C. for 1-12 hours, preferably at 25-30° C. for 8-10 hours. The Boc-protected sitagliptin free base (12) was preferably isolated by an aqueous work up procedure, preferably involving removal of N,N-dimethylformamide at 50-55° C. under reduced pressure followed by basification preferably using sodium carbonate, and extraction of the product into an organic solvent such as ethyl acetate. The Boc-protected sitagliptin free base (12) was preferably isolated by removal of the organic solvent under reduced pressure to obtain a white solid, which was preferably triturated with a non-polar solvent such as hexane.
출처 및 근거
- ORD 기록
- ord-fd4b4e18983e4755b487d5c17c657a7a
- 출처 데이터셋
- uspto-grants-2014_09
- 특허 번호
- US08846916B2
연결된 노트
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