Tetrahydrofuran → 2-(3-Chloro-4-cyanophenyl)-3-isopropyl-2,3,3a,4-tetrahydrochromeno[4,3-c]pyrazole-7-carboxylic acid

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Reaction Steps

The title compound was prepared from methyl 3-(2-methylpropylidene)-4-oxochroman-7-carboxylate; Preparation 32 (260 mg, 1.0 mmol) and 2-chloro-4-hydrazinylbenzonitrile hydrochloride; Preparation 1 (306 mg, 1.5 mmol) according to Method B and Method C. The crude product was purified by reverse-phase HPLC (30 to 95% acetonitrile/water/0.05% trifluoroacetic acid) followed by flash chromatrography (0 to 20% methanol/ethyl acetate) to give 2-(3-chloro-4-cyanophenyl)-3-isopropyl-2,3,3a,4-tetrahydrochromeno[4,3-c]pyrazole-7-carboxylic acid (yellow solid, 18.4 mg). The title compound was largely present as (±)-(3RS,3aSR)-2-(3-chloro-4-cyanophenyl)-3-isopropyl-2,3,3a,4-tetrahydrochromeno[4,3-c]pyrazole-7-carboxylic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 13.10 (br. s., 1H), 7.95 (d, J=7.8 Hz, 1H), 7.71 (d, J=8.6 Hz, 1H), 7.58 (dd, J=8.2, 1.6 Hz, 1H), 7.47 (d, J=1.2 Hz, 1H), 7.42 (d, J=2.3 Hz, 1H), 7.19 (dd, J=9.0, 1.6 Hz, 1H), 4.77-4.88 (m, 2H), 4.41 (dd, J=13.3, 10.5 Hz, 1H), 4.00-4.09 (m, 1H), 2.04-2.16 (m, 1H), 0.83 (d, J=7.0 Hz, 3H), 0.82 (d, J=7.0 Hz, 3H).

Provenance & Evidence