2-(Chloromethyl)-2-methyloxirane → 1-(3-chloro-2-hydroxy-2-methylpropyl)-N-{(S)-1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-1H-imidazole-4-carboxamide

HRID 872812Notes

Reaction equation

HRID 872812 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:14]=[CH:13][N:12]([CH2:15][C@@H:16]([NH:18][C:19]([C:21]3[N:22]=[CH:23][NH:24][CH:25]=3)=[O:20])[CH3:17])[N:11]=2)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].[Cl:26][CH2:27][C:28]1([CH3:31])[CH2:30][O:29]1>>[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:14]=[CH:13][N:12]([CH2:15][C@@H:16]([NH:18][C:19]([C:21]3[N:22]=[CH:23][N:24]([CH2:27][C:28]4([CH3:31])[CH2:30][O:29]4)[CH:25]=3)=[O:20])[CH3:17])[N:11]=2)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].[Cl:26][CH2:27][C:28]([OH:29])([CH3:31])[CH2:30][N:24]1[CH:25]=[C:21]([C:19]([NH:18][C@@H:16]([CH3:17])[CH2:15][N:12]2[CH:13]=[CH:14][C:10]([C:4]3[CH:5]=[CH:6][C:7]([C:8]#[N:9])=[C:2]([Cl:1])[CH:3]=3)=[N:11]2)=[O:20])[N:22]=[CH:23]1

Participants

4

Reactant 2

HCID 952202-(Chloromethyl)-2-methyloxiraneHCID 178461751(S)-N-{1-[3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-1H-imidazole-4-carboxamide

Product 2

HCID 671727831-(3-chloro-2-hydroxy-2-methylpropyl)-N-{(S)-1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-1H-imidazole-4-carboxamideHCID 86670259N-{(S)-1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-1-[(2-methyloxiran-2-yl)methyl]-1H-imidazole-4-carboxamide

Conditions

Temperature
120 °C

Procedure

A mixture of (S)—N-{1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-1H-imidazole-4-carboxamide (120 mg, 0.338 mmol), 2-(chloromethyl)-2-methyloxirane (2.88 g, 27.1 mmol and Y(NO3)3×6H2O (3.6 mg, 0.0093 mmol) was stirred under MW at 120° C. for 30 min. After evaporation of oxirane the residue was purified by flash chromatography on silica gel using CH2Cl2-MeOH as a gradient eluent (100:0-99:1) to obtain N-{(S)-1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-1-[(2-methyloxiran-2-yl)methyl]-1H-imidazole-4-carboxamide as a major product and 1-(3-chloro-2-hydroxy-2-methylpropyl)-N—{(S)-1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-1H-imidazole-4-carboxamide as a minor product.

Workup

  1. customAfter evaporation of oxirane the residue
  2. customwas purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-1d9adad7dd13417a830c0112e097d6d6
Source dataset
uspto-grants-2015_03
Patent number
US08975254B2

Reaction notes

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