反应详情

To a solution of methyl 2-(4-cyano-3-methylphenyl)-3-cyclopentenyl-2,3,3a,4-tetrahydrochromeno[4,3-c]pyrazole-7-carboxylate (125 mg, 0.30 mmol) in methanol (2 mL) and tetrahydrofuran (2 mL) was added 1M aqueous sodium hydroxide (2 mL). The solution was stirred for 20 hours at ambient temperature. The resulting slurry was concentrated to half volume, acidified to pH=2 with 1M hydrochloric acid and collected by vacuum filtration (yellow solid, 66 mg, 55% yield). The title compound was largely present as (±)-(3RS,3aRS)-2-(4-cyano-3-methylphenyl)-3-cyclopentenyl-2,3,3a,4-tetrahydrochromeno[4,3-c]pyrazole-7-carboxylic acid. Reversed-phase HPLC on 4.6×50 mm C-18 column, tR=2.92 minutes (10 to 90% acetonitrile/water over 4 minutes at 4 mL/minute with detection 254 nm, at 20° C.); HRMS Calculated for C24H21N3O3: 400.1656 (M+H)+. Found: 400.1678. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.61-1.87 (m, 2H), 2.03-2.13 (m, 2H), 2.17 (br. s., 2H), 2.39 (s, 3H), 3.83-3.91 (m, 1H), 3.97-4.06 (m, 1H), 4.65 (dd, J=10.20, 5.91 Hz, 1H), 5.44 (d, J=10.47 Hz, 1H), 5.60 (br. s., 1H), 6.86 (br. s., 1H), 7.11 (br. s., 1H), 7.42 (d, J=1.34 Hz, 1H), 7.53 (d, J=8.59 Hz, 1H), 7.56 (dd, J=8.19, 1.48 Hz, 1H), 7.90 (d, J=8.06 Hz, 1H), 13.12 (br. s., 1H).

1. concentrationThe resulting slurry was concentrated to half volume
2. filtrationcollected by vacuum filtration (yellow solid, 66 mg, 55% yield)
3. customon 4.6×50 mm C-18 column, tR=2.92 minutes (10 to 90% acetonitrile/water over 4 minutes at 4 mL/minute with detection 254 nm, at 20° C.)