p-Toluenesulfonic acid → HCID 58902289, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of [(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl {4-[(7-{[(3-tert-butylphenyl)amino]carbonyl}-5,6,7,8-tetrahydronaphthalen-2-yl)oxy]pyridin-2-yl}carbamate (290 mg, 0.50 mmol) and pTSA (87 mg, 0.50 mmol) in MeOH (10 mL) and water (1 mL) were heated at 70° C. for 56 h. The reaction mixture was concentrated; diluted with water, and extracted with EtOAc. The organic solutions were combined, washed with sat. aq. NaHCO3 and brine, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography to give (2S)-2,3-dihydroxypropyl {4-[(7-{[(3-tert-butylphenyl)amino]carbonyl}-5,6,7,8-tetrahydronaphthalen-2-yl)oxy]pyridin-2-yl}carbamate (I-272) (150 mg, 55%) as a white solid. 1H NMR (400 MHz, CD3OD, HCl salt) δ: 9.86 (s, 1H), 8.21 (d, 1H), 7.65-7.62 (m; 1H), 7.43-7.38 (m, 1H), 7.31-7.20 (m, 2H), 7.17-7.14 (m, 1H), 7.11-7.06 (m, 1H), 7.04-6.97 (m, 2H), 6.70-6.67 (m, 1H), 4.40-4.25 (qq, 2H), 3.91-3.85 (m, 1H), 3.60-3.56 (m, 2H), 3.15-2.79 (m, 5H), 2.24-2.16 (m, 1H), 1.99-1.88 (m, 1H), and 1.31 (s, 9H). LCMS: (FA) ES+534.3, ES−532.6.

Provenance & Evidence