Ammonia → (R)-6,6-difluoro-5-(2-fluoro-5-(pyrimidin-5-yl)phenyl)-5,7,7-trimethyl-2,5,6,7-tetrahydro-1,4-oxazepin-3-amine

HRID 331136노트

반응식

HRID 331136 반응식
[F:1][C:2]1([F:26])[C:8]([CH3:10])([CH3:9])[O:7][CH2:6][C:5](=S)[NH:4][C@@:3]1([C:13]1[CH:18]=[C:17]([C:19]2[CH:20]=[N:21][CH:22]=[N:23][CH:24]=2)[CH:16]=[CH:15][C:14]=1[F:25])[CH3:12].[NH3:27].C(OO)(C)(C)C>CO>[F:1][C:2]1([F:26])[C:8]([CH3:10])([CH3:9])[O:7][CH2:6][C:5]([NH2:27])=[N:4][C@@:3]1([C:13]1[CH:18]=[C:17]([C:19]2[CH:20]=[N:21][CH:22]=[N:23][CH:24]=2)[CH:16]=[CH:15][C:14]=1[F:25])[CH3:12]

참가 물질

5

반응물 3

HCID 222AmmoniaHCID 6410tert-Butyl hydroperoxideHCID 86671875(R)-6,6-difluoro-5-(2-fluoro-5-(pyrimidin-5-yl)phenyl)-5,7,7-trimethyl-1,4-oxazepane-3-thione

생성물 1

HCID 66558529(R)-6,6-difluoro-5-(2-fluoro-5-(pyrimidin-5-yl)phenyl)-5,7,7-trimethyl-2,5,6,7-tetrahydro-1,4-oxazepin-3-amine수율 41%

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

A solution of (R)-6,6-difluoro-5-(2-fluoro-5-(pyrimidin-5-yl)phenyl)-5,7,7-trimethyl-1,4-oxazepane-3-thione (239 mg, 627 μmol) in methanol (7.2 ml), was treated with ammonia (7 M in methanol, 5.37 ml) and tert-butyl hydroperoxide (70% in water, 517 μl). The mixture was stirred at room temperature for 16 hours. For the workup, the reaction mixture was extracted with water and dichloromethane. The organic layer was washed with water and brine, the aqueous layers were reextracted with dichloromethane. The combined organic layers were dried over sodium sulphate, filtered and evaporated to give brown oil. The residue was purified by chromatography on an amino-silica phase using dichloromethane as the eluent. The (R)-6,6-difluoro-5-(2-fluoro-5-(pyrimidin-5-yl)phenyl)-5,7,7-trimethyl-2,5,6,7-tetrahydro-1,4-oxazepin-3-amine (94 mg, 41% yield) was obtained as a white foam. MS (ISP): m/z=365.2 [M+H]+.

후처리

  1. extractionFor the workup, the reaction mixture was extracted with water and dichloromethane
  2. washThe organic layer was washed with water and brine
  3. dry with materialThe combined organic layers were dried over sodium sulphate
  4. filtrationfiltered
  5. customevaporated
  6. customto give brown oil
  7. customThe residue was purified by chromatography on an amino-silica phase

출처 및 근거

ORD 기록
ord-c075765f41e949b39b2acb42cc108357
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08877744B2

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