3-[3-(1,4-dimethyl-3H-indol-3-ylmethyl)-2-oxo-2,3-dihydro-benzimidazol-1-yl]-4-methoxy-2,2-dimethyl-butyric acid methyl ester → 3-[3-(1,4-dimethyl-3H-indol-3-ylmethyl)-2-oxo-2,3-dihydro-benzimidazol-1-yl]-4-methoxy-2,2-dimethyl-butyric acid

HRID 1747407Notes

Reaction equation

C[O:2][C:3](=[O:33])[C:4]([CH3:32])([CH3:31])[CH:5]([N:9]1[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[N:11]([CH2:18][CH:19]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][C:26]=3[CH3:28])[N:21]([CH3:29])[CH2:20]2)[C:10]1=[O:30])[CH2:6][O:7][CH3:8]>O1CCOCC1.O>[CH3:29][N:21]1[C:22]2[C:27](=[C:26]([CH3:28])[CH:25]=[CH:24][CH:23]=2)[CH:19]([CH2:18][N:11]2[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[N:9]([CH:5]([CH2:6][O:7][CH3:8])[C:4]([CH3:31])([CH3:32])[C:3]([OH:33])=[O:2])[C:10]2=[O:30])[CH2:20]1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of 3-[3-(1,4-dimethyl-3H-indol-3-ylmethyl)-2-oxo-2,3-dihydro-benzimidazol-1-yl]-4-methoxy-2,2-dimethyl-butyric acid methyl ester (50 mg, 0.11 mmol) in dioxane (2.5 ml) was added a solution of LiOH monohydrate (20 mg, 0.48 mmol) in H2O (2.5 mL). The solution was stirred at 50° C. for 16 hours. The reaction mixture was allowed to cool to rt and quenched with 4M HCl in dioxane (500 □L) and concentrated. The resulting residue was purified by CombiFlash with 3% MeOH in dichloromethane as the eluent to afford the desired 3-[3-(1,4-dimethyl-3H-indol-3-ylmethyl)-2-oxo-2,3-dihydro-benzimidazol-1-yl]-4-methoxy-2,2-dimethyl-butyric acid (15 mg, 31%). LCMS (ESMS): 436.12 (M+H+).

Workup

temperatureto cool to rt
customquenched with 4M HCl in dioxane (500 □L)
concentrationconcentrated
customThe resulting residue was purified by CombiFlash with 3% MeOH in dichloromethane as the eluent

Sources & evidence

ORD record: ord-b1882fd3992741b889be30d51053f301
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09150556B2

Reaction notes

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