Hydrochloric Acid → 6-[4-({[5-Cyclobutyl-3-(3,5-dichloro-4-pyridinyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl 6-[4-({[5-cyclobutyl-3-(3,5-dichloro-4-pyridinyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylate (53 mg, 0.095 mmol) in 2:1 tetrahydrofuran:methanol (1.5 mL) was added 1 N sodium hydroxide (0.14 mL, 0.14 mmol). The mixture was heated in a microwave reactor at 120° C. for 500 seconds and 1 N hydrochloric acid (0.14 mL, 0.14 mmol) was added. The mixture was concentrated, water was added and the mixture was extracted with ethyl acetate. The aqueous layer was extracted one more time with ethyl acetate. The combined organic layers were washed with brine and concentrated. The solid was washed with ether and dried overnight under a nitrogen stream at 45° C. to afford 6-[4-({[5-cyclobutyl-3-(3,5-dichloro-4-pyridinyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylic acid as a yellow solid (27 mg, 52%). 1H-NMR (400 MHz, DMSO-d6) δ 8.81 (s, 2H), 8.53 (d, J=9 Hz, 1H), 8.27 (s, 1H), 8.17-8.08 (m, 3H), 7.73 (d, J=9 Hz, 2H), 6.88 (d, J=9 Hz, 2H), 4.93 (s, 2H), 4.08-3.97 (m, 1H), 2.44-2.33 (m, 4H), 2.14-2.04 (m, 1H), 1.99-1.90 (m, 1H). HRMS (ESI) C29H21Cl2N3O4: 546.0982 (M+H)+, found: 546.0982 (M+H)+.

Provenance & Evidence