Water → (1-(2-(3a(r)-Benzyl-2-methyl-3-oxo-2,3,3a,4,6,7-hexahydro-pyrazolo[4,3-c]pyridin-5-yl)-1(r)-benzyloxymethyl-2-oxo-ethylcarbamoyl)-1-methyl-ethyl)-carbamic acid tert-butyl ester

HRID 986988

반응식

HRID 986988 반응식
[CH2:1]([C@:8]12[C:16](=[O:17])[N:15]([CH3:18])[N:14]=[C:13]1[CH2:12][CH2:11][NH:10][CH2:9]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([C@@H]([C@H](C([O-])=O)O)O)([O-])=O.[CH2:29]([O:36][CH2:37][CH:38]([NH:42][C:43](=[O:55])[C:44]([NH:47][C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])([CH3:46])[CH3:45])[C:39](O)=[O:40])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.O>C(OCC)(=O)C.CCCCCC>[C:51]([O:50][C:48](=[O:49])[NH:47][C:44]([C:43](=[O:55])[NH:42][C@H:38]([CH2:37][O:36][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:39]([N:10]1[CH2:11][CH2:12][C:13]2=[N:14][N:15]([CH3:18])[C:16](=[O:17])[C@:8]2([CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:9]1)=[O:40])([CH3:46])[CH3:45])([CH3:52])([CH3:53])[CH3:54]

참가 물질

7

반응물 4

HCID 962WaterHCID 119400TartrateHCID 99778733a-(r)-Benzyl-2-methyl-2,3a,4,5,6,7-hexahydro-pyrazolo[4,3-c]pyridin-3-oneHCID 129670003-Benzyloxy-2-(2-tert-butoxycarbonylamino-2-methyl-propionylamino)-propionic acid

생성물 1

HCID 11238815(1-(2-(3a(r)-Benzyl-2-methyl-3-oxo-2,3,3a,4,6,7-hexahydro-pyrazolo[4,3-c]pyridin-5-yl)-1(r)-benzyloxymethyl-2-oxo-ethylcarbamoyl)-1-methyl-ethyl)-carbamic acid tert-butyl ester수율 74.3%

시약·촉매·용매 2

HCID 8058Hexane용매HCID 8857Ethyl Acetate용매2회

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온도
0 °C

실험 절차

To a solution of 3a-(R)-benzyl-2-methyl-2,3a,4,5,6,7-hexahydro-pyrazolo[4,3-c]pyridin-3-one, L-tartrate (10.81 g, 0.0275 mol) in ethyl acetate (216.2 mL) at about −66° C. was added TEA (8.43 mL, 0.0605 mol). The mixture was stirred for about 1.5 hours. After removal of the precipitated salt by filtration, 3-benzyloxy-2-(2-tert-butoxycarbonylamino-2-methyl-propionylamino)-propionic acid (8.7 g, 0.0229 mol) and TEA (19.15 mL, 0.1374 mol) were added at about −35° C., followed by the dropwise addition of 50% PPAA in ethyl acetate (27.5 mL, 0.0458 mol). The mixture was stirred for about 2 hours at about −20° C. to about −27° C., then 1.5 hours while the temperature was slowly raised to about 0° C. The reaction mixture was poured into water and extracted with IPE, washed with 7% NaCl solution and concentrated in vacuo. The crude oil that was obtained was treated with IPE/hexane (50/50) to allow crystallization. The product was obtained as a white solid (10.3 g, yield 74.3%).

후처리

  1. customAfter removal of the precipitated salt
  2. additionwere added at about −35° C.
  3. stirringThe mixture was stirred for about 2 hours at about −20° C. to about −27° C.
  4. extractionextracted with IPE
  5. washwashed with 7% NaCl solution
  6. concentrationconcentrated in vacuo
  7. customThe crude oil that was obtained
  8. customcrystallization

출처 및 근거

ORD 기록
ord-453de6908a324fb8a3d72c5ade8fbcce
출처 데이터셋
uspto-grants-2003_10
특허 번호
US06630487B2

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