Sodium hydride → ((3S)-3-(2,2-difluoroethoxy)pyrrolidin-1-yl) (8-(1,3-oxazol-5-yl)-6-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl)methanone

HRID 931017Notes

Reaction equation

HRID 931017 reaction equation
[OH:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]([C:9]2[N:13]3[CH:14]=[C:15]([C:23]([F:26])([F:25])[F:24])[CH:16]=[C:17]([C:18]4[O:22][CH:21]=[N:20][CH:19]=4)[C:12]3=[N:11][CH:10]=2)=[O:8])[CH2:3]1.[H-].[Na+].FC(F)(F)S(O[CH2:35][CH:36]([F:38])[F:37])(=O)=O.[Cl-].[NH4+]>CN(C=O)C>[F:37][CH:36]([F:38])[CH2:35][O:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]([C:9]2[N:13]3[CH:14]=[C:15]([C:23]([F:26])([F:25])[F:24])[CH:16]=[C:17]([C:18]4[O:22][CH:21]=[N:20][CH:19]=4)[C:12]3=[N:11][CH:10]=2)=[O:8])[CH2:3]1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 27740892,2-Difluoroethyl trifluoromethanesulfonateHCID 118378931((3S)-3-Hydroxypyrrolidin-1-yl) (8-(1,3-oxazol-5-yl)-6-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl)methanone

Product 1

HCID 118399720((3S)-3-(2,2-difluoroethoxy)pyrrolidin-1-yl) (8-(1,3-oxazol-5-yl)-6-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl)methanone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

((3S)-3-Hydroxypyrrolidin-1-yl) (8-(1,3-oxazol-5-yl)-6-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl)methanone (205 mg) was dissolved in DMF (5 mL), and 60% sodium hydride (26.9 mg) and 2,2-difluoroethyl trifluoromethanesulfonate (91 μL) were added thereto at 0° C. The reaction mixture was stirred at room temperature for 2 hr, saturated aqueous ammonium chloride solution was added thereto, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane), and the obtained solid was recrystallized from ethyl acetate/hexane to give the title compound (152 mg).

Workup

  1. customat 0° C
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe extract was washed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)
  7. customthe obtained solid was recrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-ae056fd60df64bb08cfccdefbdd76811
Source dataset
uspto-grants-2016_03
Patent number
US09296746B2

Reaction notes

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