1,2-Dichloroethane → HCID 66802025, compound

Participants

Reaction Steps

A mixture of (E)-3-(4-((E)-2-(2-chloro-4-fluorophenyl)-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)but-1-en-1-yl)phenyl)acrylic acid (0.26 g, 0.5 mmol; Compound 407), DMAP (92 mg, 0.75 mmol), methane sulfonamide (0.19 g, 2 mmol) and EDC (0.14 g, 0.75 mmol) in THF (2.5 mL) was stirred at room temperature overnight. The reaction mixture was quenched with 1N HCl, diluted with water, and extracted with ethyl acetate (2×50 mL). The combined organic layers were concentrated to give the crude product that was purified on a silica gel column using 5% methanol in DCM to afford a pale yellow solid. This solid was redissolved in EtOH (5 mL), and then HCl (1 mL, 1.25 N HCl in ethanol) was added. The reaction was heated at 70° C. for 3 h, cooled to room temperature, diluted with water, and then extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with water, brine, dried over sodium sulfate, filtered, and concentrated to give the crude product. This crude material was purified on a RP-C18 column using 40-100% acetonitrile in water in the presence of 0.1% TFA to afford the title compound. 1H NMR (300 MHz, DMSO-d6): δ 13.13 (s, 1H), 11.80 (s, 1H), 8.11 (s, 1H), 7.70 (s, 1H), 7.63-7.53 (m, 2H), 7.39-7.30 (m, 4H), 7.21-7.12 (m, 2H), 7.00 (d, 2H), 6.49 (d, 1H), 3.28 (s, 3H), 2.36 (q, 2H), 0.89 (t, 3H). LCMS: 524 (M+H)+.

Provenance & Evidence