Hydrochloric Acid → HCID 178500186, compound

Participants

Reaction Conditions

Reaction Steps

(±)-Methyl 4-(5-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)-4-(5-methoxy-7-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indol-4-yl)pentanoate and (±)-methyl 4-(6-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)-4-(5-methoxy-7-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indol-4-yl)pentanoate (Example 155-K) (28 mg, 0.041 mmol) was dissolved in MeOH (700 μl) and then added 1.25 M HCl in MeOH (0.662 ml, 0.827 mmol) and heated at 65° C. After 30 minutes, an additional aliquot of 1.25 M HCl in MeOH (0.993 ml, 1.241 mmol) was added along with MeOH (700 uL) and the reaction left stirring for 17 hours. At this point an additional aliquot of 1.25 M HCl in MeOH (1.5 ml, 1.875 mmol) was added the reaction was heated at 75° C. for 3 hours and after additional 1.25 M HCl in MeOH (1.5 ml, 1.875 mmol) was added, the temperature was increased 85° C. and the reaction stirred for further 4 hours. At this point, an additional aliquot of 1.25 M HCl in MeOH (3 ml, 3.75 mmol) was added and the reaction was heated at 90° C. for 2 h. The reaction was then cooled to 0° C. and quenched with saturated sodium bicarbonate until pH=7 and then diluted with EtOAc. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organics were dried over sodium sulfate and then concentrated. The resulting residue was absorbed onto silica to purify via FCC (0-60% EtOAc:heptanes) to obtain the title compound. MS (ESI+) m/z 417.18 (M+H).

Provenance & Evidence