Hydrogen chloride-ethyl acetate → N-((2S)-1-((2-(4-(2-(2,2-difluorocyclopropyl)ethoxy)phenyl)[1,3]oxazolo[4,5-c]pyridin-6-yl)oxy)propan-2-yl)acetamide

HRID 2277340Notes

Reaction equation

HRID 2277340 reaction equation
[F:1][C:2]1([F:35])[CH2:4][CH:3]1[CH2:5][CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[O:15][C:16]3[CH:21]=[C:20]([O:22][CH2:23][C@@H:24]([NH:26][C:27](=O)[O:28]C(C)(C)C)[CH3:25])[N:19]=[CH:18][C:17]=3[N:34]=2)=[CH:10][CH:9]=1.Cl.[C:37](OCC)(=O)C>C(OCC)(=O)C>[F:35][C:2]1([F:1])[CH2:4][CH:3]1[CH2:5][CH2:6][O:7][C:8]1[CH:9]=[CH:10][C:11]([C:14]2[O:15][C:16]3[CH:21]=[C:20]([O:22][CH2:23][C@@H:24]([NH:26][C:27](=[O:28])[CH3:37])[CH3:25])[N:19]=[CH:18][C:17]=3[N:34]=2)=[CH:12][CH:13]=1

Participants

4

Reactant 2

HCID 21866389Hydrogen chloride-ethyl acetateHCID 86731429tert-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

Product 1

HCID 86731430N-((2S)-1-((2-(4-(2-(2,2-difluorocyclopropyl)ethoxy)phenyl)[1,3]oxazolo[4,5-c]pyridin-6-yl)oxy)propan-2-yl)acetamide

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 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 (239 mg), 4M hydrogen chloride/ethyl acetate (3 mL) and ethyl acetate (3 mL) was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure, and the obtained residue was mixed with acetic anhydride (0.138 mL) and pyridine (3 mL), and the obtained mixture was stirred at room temperature for 1 hr. To the reaction mixture was added 1M hydrochloric acid, 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 recrystallized (ethyl acetate) to give the title compound (155 mg).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionthe obtained residue was mixed with acetic anhydride (0.138 mL) and pyridine (3 mL)
  3. stirringthe obtained mixture was stirred at room temperature for 1 hr
  4. additionTo the reaction mixture was added 1M hydrochloric acid
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe combined organic layer were washed with saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customthe solvent was evaporated under reduced pressure
  9. customThe residue was recrystallized (ethyl acetate)

Sources & evidence

ORD record
ord-f885ef1168004dad92d86c9b3274c28d
Source dataset
uspto-grants-2015_09
Patent number
US09133129B2

Reaction notes

Loading…