Epichlorohydrin → HCID 118522918, compound

HRID 529847Notes

Reaction equation

HRID 529847 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:25][CH:26]([F:28])[F:27])=[C:6]([C:8]2[C:12]([NH:13][C:14]([C:16]3[CH:17]=[N:18][N:19]4[CH:24]=[CH:23][CH:22]=[N:21][C:20]=34)=[O:15])=[CH:11][NH:10][N:9]=2)[CH:7]=1.C([O-])([O-])=O.[Cs+].[Cs+].Cl[CH2:36][CH:37]1[CH2:39][O:38]1>CN(C)C=O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:25][CH:26]([F:28])[F:27])=[C:6]([C:8]2[C:12]([NH:13][C:14]([C:16]3[CH:17]=[N:18][N:19]4[CH:24]=[CH:23][CH:22]=[N:21][C:20]=34)=[O:15])=[CH:11][N:10]([CH2:36][CH:37]3[CH2:39][O:38]3)[N:9]=2)[CH:7]=1

Participants

6

Reactant 3

HCID 7835EpichlorohydrinHCID 10796Cesium carbonateHCID 178522413HCID 178522413, compound

Product 1

HCID 118522918HCID 118522918, compoundYield 44%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide (1.00 g, 2.47 mmol) in N,N-dimethylformamide (10 mL), Cs2CO3 (970 mg, 2.977 mmol) was added and stirred for 10 minutes at room temperature. Then 2-(chloromethyl)oxirane (2.28 g, 24.64 mmol) was added dropwise at room temperature. The resulting mixture was stirred for 14 hour at room temperature and diluted with ethyl acetate (100 mL), washed with water and brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by flash chromatography on silica gel eluting with ethyl acetate/petroleum ether (60/40) to give 500 mg (44%) of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-(oxiran-2-ylmethyl)-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide as a light yellow solid. LCMS (Method 24), [M+H]+=461.1, RT=1.30 min.

Workup

  1. stirringThe resulting mixture was stirred for 14 hour at room temperature
  2. washwashed with water and brine
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated under vacuum
  5. customThe residue was purified by flash chromatography on silica gel eluting with ethyl acetate/petroleum ether (60/40)

Sources & evidence

ORD record
ord-242bdfb6bee44b53bd920da37b5e0058
Source dataset
uspto-grants-2016_05
Patent number
US09346815B2

Reaction notes

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