Propylphosphonic anhydride → N-(3-((1R,5S,6R)-3-amino-5-(difluoromethyl)-2-oxa-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-5-chloro-3-methoxypicolinamide

HRID 1526641노트

반응식

HRID 1526641 반응식
CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O.[NH2:19][C:20]1[CH:21]=[CH:22][C:23]([F:37])=[C:24]([C@@:26]2([CH:34]([F:36])[F:35])[C@H:32]3[C@H:30]([CH2:31]3)[O:29][C:28]([NH2:33])=[N:27]2)[CH:25]=1.[Cl:38][C:39]1[CH:40]=[C:41]([O:48][CH3:49])[C:42]([C:45](O)=[O:46])=[N:43][CH:44]=1>C([O-])(O)=O.[Na+]>[NH2:33][C:28]1[O:29][C@H:30]2[C@@H:32]([C@:26]([C:24]3[CH:25]=[C:20]([NH:19][C:45](=[O:46])[C:42]4[C:41]([O:48][CH3:49])=[CH:40][C:39]([Cl:38])=[CH:44][N:43]=4)[CH:21]=[CH:22][C:23]=3[F:37])([CH:34]([F:35])[F:36])[N:27]=1)[CH2:31]2

참가 물질

5

반응물 3

HCID 111923Propylphosphonic anhydrideHCID 840704685-Chloro-3-methoxy-pyridine-2-carboxylic acidHCID 90414662(1S,5R,6S)-5-(5-amino-2-fluorophenyl)-5-(difluoromethyl)-2-oxa-4-azabicyclo[4.1.0]hept-3-en-3-amine

생성물 1

HCID 118232930N-(3-((1R,5S,6R)-3-amino-5-(difluoromethyl)-2-oxa-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-5-chloro-3-methoxypicolinamide수율 67.3%

시약·촉매·용매 1

HCID 516892Sodium Bicarbonate용매

실험 절차

A solution of 1-propanephosphonic acid cyclic anhydride (50 wt % in EtOAc, 0.352 ml, 0.553 mmol) was added to a solution of (1R,5S,6R)-5-(5-amino-2-fluorophenyl)-5-(difluoromethyl)-2-oxa-4-azabicyclo[4.1.0]hept-3-en-3-amine (16g-B, 0.075 g, 0.277 mmol) and 5-chloro-3-methoxypicolinic acid (0.062 g, 0.332 mmol) in EtOAC (2 mL) at room temperature. The reaction mixture was stirred at rt for 12 h, diluted with aqueous saturated NaHCO3 solution and extracted with EtOAC. The organic phase dried over MgSO4 and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography using (0-100% EtOAc/heptane) to give the title compound (0.082 g, 0.186 mmol, 67.3% yield). MS m/z=441.1 [M+H]+

후처리

  1. extractionextracted with EtOAC
  2. dry with materialThe organic phase dried over MgSO4
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. customThe residue was purified by silica gel chromatography

출처 및 근거

ORD 기록
ord-5b108c72aaf441b28ae9824357aef27b
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09085576B2

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