Pyridine → 1,1-dimethylethyl 3-({[3-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-({(1S)-2-[(difluoromethyl)oxy]-1-methylethyl}oxy)phenyl]carbonyl}amino)-1H-pyrazole-1-carboxylate

HRID 1011824Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1011824
ClC(N(C)C)=C(C)C.[N:9]1([C:13]([C:15]2[N:16]=[CH:17][C:18]([O:21][C:22]3[CH:23]=[C:24]([CH:28]=[C:29]([O:31][C@@H:32]([CH3:38])[CH2:33][O:34][CH:35]([F:37])[F:36])[CH:30]=3)[C:25](O)=[O:26])=[N:19][CH:20]=2)=[O:14])[CH2:12][CH2:11][CH2:10]1.[NH2:39][C:40]1[CH:44]=[CH:43][N:42]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[N:41]=1.N1C=CC=CC=1>C(Cl)Cl.O.C(OCC)(=O)C>[N:9]1([C:13]([C:15]2[N:16]=[CH:17][C:18]([O:21][C:22]3[CH:23]=[C:24]([C:25]([NH:39][C:40]4[CH:44]=[CH:43][N:42]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[N:41]=4)=[O:26])[CH:28]=[C:29]([O:31][C@@H:32]([CH3:38])[CH2:33][O:34][CH:35]([F:37])[F:36])[CH:30]=3)=[N:19][CH:20]=2)=[O:14])[CH2:10][CH2:11][CH2:12]1

Komponenten

8

Edukt 4

HCID 1049PyridineHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 51358380tert-Butyl 3-amino-1H-pyrazole-1-carboxylateHCID 591271903-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-({(1S)-2-[(difluoromethyl)oxy]-1-methylethyl}oxy)benzoic acid

Produkt 1

HCID 591271291,1-dimethylethyl 3-({[3-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-({(1S)-2-[(difluoromethyl)oxy]-1-methylethyl}oxy)phenyl]carbonyl}amino)-1H-pyrazole-1-carboxylateAusbeute 27,9 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

1-Chloro-N,N,2-trimethyl-1-propenylamine (0.12 mL, 0.92 mmol) was added to a solution of 3-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-({(1S)-2-[(difluoromethyl)oxy]-1-methylethyl}oxy)benzoic acid (0.26 g, 0.61 mmol) in DCM (8 mL) and stirred for 1 hour. 1,1-Dimethylethyl 3-amino-1H-pyrazole-1-carboxylate (169 mg, 0.92 mmol) then pyridine (0.1 mL, 1.23 mmol) were added and stirred for a further 20 hours. The reaction mixture was reduced in vacuo and ethyl acetate (50 mL) and water (50 mL) were added. The aqueous layer was re-extracted into ethyl acetate (50 mL) and the combined organics washed with water (50 mL), brine (50 mL), dried (MgSO4), filtered and reduced in vacuo. The crude oil was chromatographed on silica, eluting with 25-50% ethyl acetate in isohexane, to give the desired compound as a colourless oil (100 mg).

Aufarbeitung

  1. stirringstirred for a further 20 hours
  2. additionwere added
  3. extractionThe aqueous layer was re-extracted into ethyl acetate (50 mL)
  4. washthe combined organics washed with water (50 mL), brine (50 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customThe crude oil was chromatographed on silica
  8. washeluting with 25-50% ethyl acetate in isohexane

Quellen und Nachweise

ORD-Eintrag
ord-c1752faeeccf45698cc5177dcac01e8e
Quelldatensatz
uspto-grants-2011_07
Patentnummer
US07977328B2

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