Hydrochloric Acid → HCID 86703583, compound

Participants

Reaction Steps

A degassed mixture of N-(azetidin-1-ylsulfonyl)-5-chloro-2-fluoro-4-((3-(hydroxymethyl)adamantan-1-yl)methoxy)benzamide (0.51 g, 1.04 mmol), cyclopropylboronic acid (0.89 g, 10.4 mmol), tricyclohexylphosphine tetrafluoroborate (0.23 g, 0.62 mmol), potassium phosphate (tribasic, 1.10 g, 5.20 mmol), water (3.0 mL), and tetrahydrofuran (3.0 mL) in toluene (15 mL) was added palladium (II) acetate (0.070 g, 0.31 mmol). The resulting mixture was refluxed under nitrogen for 18 hours. The reaction mixture was cooled to ambient temperature and added additional cyclopropylboronic acid (0.89 g, 10.40 mmol), tricyclohexylphosphine tetrafluoroborate (0.23 g, 0.62 mmol), and potassium phosphate (tribasic, 1.10 g, 5.20 mmol), and then refluxed under nitrogen for 10 hours. The reaction mixture was cooled to ambient temperature and diluted with ethyl acetate (80 mL) and water (50 mL), acidified with 1 M aqueous hydrochloric acid solution. The organic layer was washed with 1 M aqueous hydrochloric acid solution (20 mL) and brine (2×50 mL); dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (1:1 hexanes:ethyl acetate (+0.2% acetic acid v/v)) to provide the title compound (0.27 g, 53%): 1H NMR (300 MHz, DMSO-d6) δ 11.56 (br s, 1H), 7.11 (d, J=8.5 Hz, 1H), 6.90 (d, J=13.0 Hz, 1H), 4.38-4.31 (m, 1H), 4.01 (t, J=7.5 Hz, 4H), 3.64 (s, 2H), 3.02-2.96 (m, 2H), 2.19-2.06 (m, 2H), 2.06-1.94 M, 3H), 1.64-1.47 (m, 6H), 1.45-1.32 (m, 6H), 0.92-0.83 (m, 2H), 0.96-0.61 (m, 2H); MS (ES+) m/z 493.2 (M+1).

Provenance & Evidence