Methyl 2-bromopropionate → HCID 86701757, compound

Participants

Reaction Steps

To tert-Butyl 4-((5-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate and tert-butyl 4-((6-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (Example 145-A) (850 mg, 1.55 mmol) in THF (20 mL) at −78° C. was added 1 M LHMDS in THF (4.6 mL, 4.6 mmol) and the reaction was stirred for 30 minutes. Methyl 2-bromopropanoate (1.72 mL, 15.5 mmol) was then added and the reaction was allowed to stir at room temperature for 2 hours. The mixture was poured into a saturated aq. solution of NaHCO3 (80 mL) and extracted with ethyl acetate, dried over sodium sulfate, concentrated, and purified via preparative HPLC(X-terra MS, C18 column, 20 mL/min) to obtain (±)-tert-butyl 4-(1-(5-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)-3-methoxy-2-methyl-3-oxopropyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate and (±)-tert-butyl 4-(1-(6-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)-3-methoxy-2-methyl-3-oxopropyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate as a single diastereomer (diastereomer A, tr=16.9 min) and (±)-tert-butyl 4-(1-(5-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)-3-methoxy-2-methyl-3-oxopropyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate and (±)-tert-butyl 4-(1-(6-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)-3-methoxy-2-methyl-3-oxopropyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate as a single diastereomer (diastereomer B, tr=18.7 min). MS (ESI+) m/z 633.2 (M+H).

Provenance & Evidence