Hydrochloric Acid → 3-cyclopentyl-2-[4-(1H-indol-4-yloxy)-6-oxo-6H-pyridazin-1-yl]-propionic acid

Participants

Reaction Conditions

Reaction Steps

A solution of 3-cyclopentyl-2-[4-(1H-indol-4-yloxy)-6-oxo-6H-pyridazin-1-yl]-propionic acid methyl ester (500 mg, 1.3 mmol) in methanol (3 mL) was treated with a 4N aqueous sodium hydroxide solution (63 mg, 1.57 mmol). The reaction solution was stirred at 25° C. overnight. At this time, the reaction mixture was diluted with water (10 mL) and was acidified with a 1N aqueous hydrochloric acid solution until pH=2. The aqueous phase was extracted with ethyl acetate (3×20 mL). The combined organics were washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Chromatography afforded 3-cyclopentyl-2-[4-(1H-indol-4-yloxy)-6-oxo-6H-pyridazin-1-yl]-propionic acid as an off-white solid (0.2 g, 42%); LC-MS: 368 [M+1]+, tR=4.21 min. Purity on HPLC: 95.1% (254 nm), 96.6% (214 nm), tR=7.26 min. 1H NMR (300 MHz, CDCl3): δ 13.00 (s, 1H), 11.50 (s, 1H), 8.17 (d, 1H, J=2.4 Hz), 7.42 (d, 2H, J=7.8 Hz), 7.17 (t, 1H, J=7.8 Hz), 6.89 (d, 1H, J=7.8 Hz), 6.26 (s, 1H), 5.63 (d, 1H, J=2.4 Hz), 5.31 (dd, 1H, J1=10.5 Hz, J2=4.2 Hz), 2.23˜2.13 (m, 1H), 2.02˜1.94 (m, 1H), 1.59˜1.44 (m, 7H), 1.18˜1.04 (m, 2H).

Provenance & Evidence