(6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-1H-benzo[d]imidazol-4-yl)(pyridin 2-yl)methanone → 4-(cyclopentyl(hydroxy)(pyridin-2-yl)methyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-benzo[d]imidazol-2(3H)-one

HRID 1773732Notes

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]CC)[NH:12][C:11]=3[CH:18]=2)=[C:5]([CH3:27])[O:4][N:3]=1.[CH:28]1([Mg]Cl)[CH2:32][CH2:31][CH2:30][CH2:29]1>C1COCC1>[CH:28]1([C:19]([OH:20])([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=2)[C:9]2[C:10]3[NH:14][C:13](=[O:15])[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)[CH2:32][CH2:31][CH2:30][CH2:29]1

Participants

Conditions

Temperature: 0 °C

Procedure

(6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-1H-benzo[d]imidazol-4-yl)(pyridin-2-yl)methanone (50 mg, 0.14 mmol) was dissolved in dry THF (1.4 mL) under argon and cooled to 0° C. Cyclopentylmagnesium chloride (2.0 M, 0.14 mL, 0.28 mmol) was added dropwise and reaction was allowed to stir for 10 minutes then quenched with water. Reaction mixture was extracted three times with EtOAc and combined organic layers were washed once with water and concentrated. Residue was taken up in EtOH (1.5 mL) and 4.0M HCl/dioxane (0.75 mL) and heated to 65° C. for 2 hours. Reaction was concentrated and purified by reverse-phase HPLC to afford the desired product as a white powder.

Workup

customreaction
customthen quenched with water
customReaction mixture
extractionwas extracted three times with EtOAc
washwere washed once with water
concentrationconcentrated
temperature4.0M HCl/dioxane (0.75 mL) and heated to 65° C. for 2 hours
customReaction
concentrationwas concentrated
custompurified by reverse-phase HPLC

Sources & evidence

ORD record: ord-1f85a9efd1044126a1463adb1a25cac1
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09255089B2

Reaction notes

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