(6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-1H-benzo[d]imidazol-4-yl)(pyridin 2-yl)methanone → cyclopropyl(6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-1H-benzo[d]imidazol-4-yl)(pyridin-2-yl)methanol

HRID 1773730Notes

Reaction equation

HRID 1773730 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[CH:8]=[C:9]([C:19]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=3)=[O:20])[C:10]3[N:14]=[C:13]([O:15][CH2:16][CH3:17])[NH:12][C:11]=3[CH:18]=2)=[C:5]([CH3:27])[O:4][N:3]=1.[CH:28]1([Mg]Br)[CH2:30][CH2:29]1>C1COCC1>[CH:28]1([C:19]([C:9]2[C:10]3[N:14]=[C:13]([O:15][CH2:16][CH3:17])[NH:12][C:11]=3[CH:18]=[C:7]([C:6]3[C:2]([CH3:1])=[N:3][O:4][C:5]=3[CH3:27])[CH:8]=2)([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=2)[OH:20])[CH2:30][CH2:29]1

Participants

4

Reactant 2

HCID 117601753(6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-1H-benzo[d]imidazol-4-yl)(pyridin 2-yl)methanoneHCID 178418630HCID 178418630, compound

Product 1

HCID 117601196cyclopropyl(6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-1H-benzo[d]imidazol-4-yl)(pyridin-2-yl)methanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-1H-benzo[d]imidazol-4-yl)(pyridin-2-yl)methanone (40 mg, 0.11 mmol) was dissolved in dry THF (1.1 mL) and cyclopropylmagnesium bromide (0.5 M in diethylether, 1.1 mL, 0.55 mmol) was added dropwise at rt and the reaction was allowed to stir for 10 minutes. The reaction was quenched with water, concentrated, and purified by reverse-phase HPLC to give cyclopropyl(6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-1H-benzo[d]imidazol-4-yl)(pyridin-2-yl)methanol intermediate which was taken up in 1.0 mL EtOH and 0.7 mL 4.0M HCl/dioxane and heated for 2 hours at 65° C. Reaction was then concentrated down and purified by reverse-phase HPLC to afford the desired product as a white powder.

Workup

  1. customThe reaction was quenched with water
  2. concentrationconcentrated
  3. custompurified by reverse-phase HPLC

Sources & evidence

ORD record
ord-d4048c7f75854e8fa82784464d1feed3
Source dataset
uspto-grants-2016_02
Patent number
US09255089B2

Reaction notes

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