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Dimethylformamide → tert-butyl ((2S)-1-((2-(4-(2-(2,2-difluorocyclopropyl)ethoxy)phenyl)[1,3]oxazolo[4,5-c]pyridin-6-yl)oxy)propan-2-yl)carbamate

HRID 2277339
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 2277339
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:15]=[C:14]([O:16][CH2:17][C@@H:18]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH3:19])[N:13]=[CH:12][C:11]=3[N:28]=2)=[CH:4][CH:3]=1.CS(O[CH2:34][CH2:35][CH:36]1[CH2:38][C:37]1([F:40])[F:39])(=O)=O.C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>O>[F:39][C:37]1([F:40])[CH2:38][CH:36]1[CH2:35][CH2:34][O:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:15]=[C:14]([O:16][CH2:17][C@@H:18]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:24])([CH3:26])[CH3:25])[CH3:19])[N:13]=[CH:12][C:11]=3[N:28]=2)=[CH:4][CH:3]=1
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Komponenten

6

Edukt 4

HCID 6228DimethylformamideHCID 11430Potassium Carbonate2×HCID 866663152-(2,2-Difluorocyclopropyl)ethyl methanesulfonate2×HCID 136341411tert-butyl ((2S)-1-((2-(4-hydroxyphenyl)[1,3]oxazolo[4,5-c]pyridin-6-yl)oxy)propan-2-yl)carbamate

Produkt 1

HCID 86731429
tert-butyl ((2S)-1-((2-(4-(2-(2,2-difluorocyclopropyl)ethoxy)phenyl)[1,3]oxazolo[4,5-c]pyridin-6-yl)oxy)propan-2-yl)carbamate
Ausbeute 62,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

A mixture of tert-butyl ((2S)-1-((2-(4-hydroxyphenyl)[1,3]oxazolo[4,5-c]pyridin-6-yl)oxy)propan-2-yl)carbamate (300 mg), 2-(2,2-difluorocyclopropyl)ethyl methanesulfonate (312 mg), potassium carbonate (215 mg) and DMF (5 mL) was stirred overnight at 70° C. The reaction mixture was allowed to cool to room temperature, and 2-(2,2-difluorocyclopropyl)ethyl methanesulfonate (935 mg) and potassium carbonate (645 mg) were added thereto. The obtained mixture was stirred overnight at 70° C. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The combined organic layer were washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (239 mg).

Aufarbeitung

  1. temperatureto cool to room temperature
  2. stirringThe obtained mixture was stirred overnight at 70° C
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe combined organic layer were washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-307c3c99b3414dad94c805b8b68aedf3
Quelldatensatz
uspto-grants-2015_09
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09133129B2

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