Hydrochloric Acid → HCID 59146021, compound

Participants

Reaction Steps

Potassium hydroxide (90 mg) was added to a solution of ethyl 3-[7-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-5-fluoro-1H-indol-3-yl]propanoate (D139) (189 mg) and iodomethane (0.25 mL) in DMSO (3 mL) at RT. The reaction mixture was stirred at RT for 5 hours. Then the reaction was quenched with saturated ammonium chloride, and extracted with EA for 3 times. The combined organic solution was washed with brine and dried over anhydrous sodium sulfate. The dried solution was concentrated to afford the crude product as a yellow oil. This oil was dissolved in THF (3 mL) and water (3 mL). Sodium hydroxide (40 mg) was then added to the mixture. The reaction mixture was stirred at 90° C. for 1 hour, and at RT for another 24 hours. Then 0.5 M HCl was added until pH was about 6. The solvent was concentrated, and the residue was dissolved in water. The precipitated solid was purified by MDAP to afford 3-[7-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-5-fluoro-1-methyl-1H-indol-3-yl]propanoic acid (E102) (112 mg) as an off-white solid. δH (DMSO-d6, 400 MHz): 1.38 (6H, d), 2.58 (2H, t), 2.93 (2H, t), 3.62 (3H, s), 5.42-5.48 (1H, m), 7.29 (1H, s), 7.30 (1H, dd), 7.65 (1H, dd), 8.59 (1H, d), 8.96 (1H, d), 12.13 (1H, br s). δF (DMSO-d6, 376 MHz): −125.6. MS (ES): C22H20ClFN4O4 requires 458; found 459.1 (M+H+).

Provenance & Evidence