Chlorotrimethylsilane → (R)-N,N-dimethyl-2-(2-neopentyl-5-(pyrrolidin-3-ylsulfonyl)-1H-benzo[d]imidazol-1-yl)ethanamine

HRID 241674Notes

Reaction equation

[CH3:1][N:2]([CH3:34])[CH2:3][CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][C:12]([S:14]([C@@H:17]3[CH2:21][CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18]3)(=[O:16])=[O:15])=[CH:13][C:8]=2[N:7]=[C:6]1[CH2:29][C:30]([CH3:33])([CH3:32])[CH3:31].Cl[Si](C)(C)C>CO>[CH3:1][N:2]([CH3:34])[CH2:3][CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][C:12]([S:14]([C@@H:17]3[CH2:21][CH2:20][NH:19][CH2:18]3)(=[O:15])=[O:16])=[CH:13][C:8]=2[N:7]=[C:6]1[CH2:29][C:30]([CH3:32])([CH3:31])[CH3:33]

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of (R)-tert-butyl 3-(1-(2-(dimethylamino)ethyl)-2-neopentyl-1H-benzo[d]imidazol-5-ylsulfonyl)pyrrolidine-1-carboxylate (STEP B, 612 mg, 1.24 mmol) in methanol (5 mL) was added chlorotrimethylsilane (749 microL, 6.21 mmol). The mixture was stirred at 50° C. for 3 h. The mixture was concentrated in vacuo. To the residue was added 2 mol/L sodium hydroxide aqueous solution to pH>7 and the mixture was extracted with ethyl acetate (150 mL). The organic layer was washed with brine and dried over sodium sulfate. The resulting solution was concentrated to give the title compound (453 mg, 93%) as an oil.

Workup

concentrationThe mixture was concentrated in vacuo
additionTo the residue was added 2 mol/L sodium hydroxide aqueous solution to pH>7
extractionthe mixture was extracted with ethyl acetate (150 mL)
washThe organic layer was washed with brine
dry with materialdried over sodium sulfate
concentrationThe resulting solution was concentrated

Sources & evidence

ORD record: ord-d519c11abe5146429d739ddd8bed1bf6
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653063B2

Reaction notes

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