Hydrochloric Acid → HCID 178483016, compound

Participants

Reaction Conditions

Reaction Steps

To a mixture of (±)-tert-butyl 4-(1-(5-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)-2,2,2-trifluoro-1-hydroxyethyl)-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)-2,2,2-trifluoro-1-hydroxyethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (Example 33-A) (1.27 g, 2.014 mmol) was added 1.25 M HCl in MeOH (16.11 mL, 20.14 mmol) and the mixture was stirred at 60° C. After 40 minutes the reaction was cooled to room temperature and concentrated. The mixture was dissolved in CHCl3 (40 mL), then was added thionyl chloride (1.47 mL, 20.14 mmol) and DMF (0.5 mL) and the mixture was heated at 70° C. After 10 minutes the reaction was cooled to room temperature and concentrated. At this point the reaction was dissolved in 33% methylamine in EtOH (25 mL, 201 mmol) and stirred at room temperature. After 5 minutes the mixture was concentrated and the resulting residue was purified directly by flash chromatography (0-100% EtOAc in heptanes) to provide (±)-tert-butyl 4-(1-(5-cyano-1H-benzo[d]imidazol-2-yl)-2,2,2-trifluoro-1-(methylamino)ethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate. MS (ESI+) m/z 514.3 (M+H). In addition, (±)-tert-butyl 4-(1-(5-cyano-1H-benzo[d]imidazol-2-yl)-1-(dimethylamino)-2,2,2-trifluoroethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate was also isolated. MS (ESI−) m/z 526.3 (M−H).

Provenance & Evidence