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 1526641ノート

反応式

HRID 1526641 の反応式
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

参加物

5

反応物 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

生成物 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-methoxypicolinamide収率 67.3%

試薬・触媒・溶媒 1

HCID 516892Sodium Bicarbonate溶媒

実験手順

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]+

後処理

  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

出典と根拠

ORDレコード
ord-5b108c72aaf441b28ae9824357aef27b
出典データセット
uspto-grants-2015_07
特許番号
US09085576B2

反応ノート

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