p-Toluenesulfonic acid → HCID 349055, compound

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Reaction Steps

A mixture of 7-{[2-(acetylamino)pyridin-4-yl]oxy}-N-[3-{[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy}-5-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydronaphthalene-2-carboxamide (100 mg, 0.16 mmol) and pTSA (28 mg, .16 mmol) in MeOH (7 mL) and water (1 mL) was allowed to stir at rt overnight and then at 70° C. Water was added and the mixture was 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 7-{[2-(acetylamino)pyridin-4-yl]oxy}-N-3-{[(2R)-2,3-dihydroxypropyl]-oxy}-5-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydronaphthalene-2-carboxamide (I-412) (80 mg, 68%) as a white solid. 1H NMR (400 MHz, d6-DMSO, HCl salt) δ: 10.52 (s, 1H), 8.24 (d, 1H), 7.66 (br s, 1H), 7.56 (br s, 1H), 7.29-7.17 (m, 2H), 7.06-6.86 (m, 4H), 4.07-3.75 (m, 3H), 3.46-3.40 (m, 2H), 3.00-2.74 (m, 5H), 2.19-2.05 (m, 4H), and 1.89-1.71 (m, 1H). LCMS: (FA) ES+560.1, ES−558.0.

Provenance & Evidence