Sodium Bicarbonate → 2-(trimethylsilyl)ethyl (1S,2R,3S,5S)-2-(6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-ylamino)bicyclo[3.1.0]hexan-3-ylcarbamate

HRID 56371

반응식

HRID 56371 반응식
[NH2:1][C@H:2]1[C@@H:7]([NH:8][C:9](=[O:17])[O:10][CH2:11][CH2:12][Si:13]([CH3:16])([CH3:15])[CH3:14])[CH2:6][C@H:5]2[C@@H:3]1[CH2:4]2.Cl[C:19]1[N:28]=[CH:27][C:26]2[C:21](=[CH:22][CH:23]=[C:24]([C:29]3[C:34]([Cl:35])=[C:33]([O:36][CH3:37])[CH:32]=[C:31]([O:38][CH3:39])[C:30]=3[Cl:40])[CH:25]=2)[N:20]=1.C(=O)(O)[O-].[Na+]>CN1CCCC1=O.C(OCC)(=O)C>[Cl:35][C:34]1[C:33]([O:36][CH3:37])=[CH:32][C:31]([O:38][CH3:39])=[C:30]([Cl:40])[C:29]=1[C:24]1[CH:25]=[C:26]2[C:21](=[CH:22][CH:23]=1)[N:20]=[C:19]([NH:1][C@H:2]1[C@@H:7]([NH:8][C:9](=[O:17])[O:10][CH2:11][CH2:12][Si:13]([CH3:14])([CH3:16])[CH3:15])[CH2:6][C@H:5]3[C@@H:3]1[CH2:4]3)[N:28]=[CH:27]2

참가 물질

6

반응물 3

HCID 516892Sodium BicarbonateHCID 899217722-Chloro-6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolineHCID 1317369152-trimethylsilylethyl N-[(1S,2R,3S,5S)-2-amino-3-bicyclo[3.1.0]hexanyl]carbamate

생성물 1

HCID 1317369142-(trimethylsilyl)ethyl (1S,2R,3S,5S)-2-(6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-ylamino)bicyclo[3.1.0]hexan-3-ylcarbamate수율 62.5%

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 13387N-methyl-2-pyrrolidone용매

실험 절차

A solution of 2-(trimethylsilyl)ethyl (1S,2R,3S,5S)-2-aminobicyclo[3.1.0]hexan-3-ylcarbamate (250 mg, 0.977 mmol), 2-chloro-6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazoline (300 mg, 0.814 mmol) and sodium bicarbonate (205 mg, 2.442 mmol) in N-methyl-2-pyrrolidone (10 mL) was stirred at 100° C. overnight. The reaction solution was cooled to room temperature, diluted with ethyl acetate (100 mL) and washed with water (eight times) and brine (50 mL). The organic layer was dried over sodium sulfate, filtered and concentrated to afford a crude product, which was purified by silica gel column chromatography (ethyl acetate:petroleum ether=4:2) to afford the title compound (300 mg, 52%) as a yellow solid. MS (ES+) C28H34Cl2N4O4Si requires: 588, 590, found: 589, 591 [M+H]+.

후처리

  1. washwashed with water (eight times) and brine (50 mL)
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto afford a crude product, which
  6. customwas purified by silica gel column chromatography (ethyl acetate:petroleum ether=4:2)

출처 및 근거

ORD 기록
ord-ea6964527a4d4262afbdc8f164fae667
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09434700B2

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