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 1526641Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1526641
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

Komponenten

5

Edukt 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

Produkt 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-methoxypicolinamideAusbeute 67,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 516892Sodium BicarbonateLösungsmittel

Versuchsvorschrift

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]+

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-5b108c72aaf441b28ae9824357aef27b
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09085576B2

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