Water → HCID 58902348, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of N-(3-tert-butylphenyl)-7-{[2-(methylamino)pyridin-4-yl]oxy}-1,2,3,4-tetrahydronaphthalene-2-carboxamide (337 mg, 0.78 mmol) in THF (8 mL) was added TEA (0.219 mL, 1.57 mmol). The reaction mixture was cooled to 0° C. and acetyl chloride (0.062 mL, 0.86 mmol) was added dropwise. The reaction mixture was allowed to stir at 0° C. for 5 hr. during which time further portions of TEA (0.219 mL, 1.57 mmol) and acetyl chloride (0.62 mL, 0.86 mmol) were added. Water was added and the mixture was extracted with EtOAc. The organic solutions were combined, washed with water and brine, dried over Na2SO4 and concentrated. The residue was purified by column chromatography. The product was further purified by HPLC (250 mm C18 column) eluting with 40% A/60% B to 100%/0% B (25 min gradient) (A=99/1 H2O in AcCN, 0.1% FA, B=95/5 AcCN/H2O, 0.1% FA). The product was dissolved in DCM and MeOH and 2M HCl-Et2O solution was added. The solvents were evaporated to provide 7-({2-[acetyl(methyl)amino]pyridin-4-yl}oxy)-N-(3-tert-butylphenyl)-1,2,3,4-tetrahydronaphthalene-2-carboxamide I-395 as the HCl salt (22 mg, 5.4%). 1H NMR (300 MHz, d6-DMSO, HCOOH Salt) δ: 9.94 (s, 1H), 8.31 (d, 1H), 7.63 (t, 1H), 7.50 (d, 1H), 7.24-7.18 (m, 2H), 7.10-7.05 (m, 2H), 6.76 (dd, 3H), 3.24 (s, 3H), 2.95-2.71 (m, 5H), 2.13-1.99 (m, 4H), 1.85-1.72 (m, 1H), and 1.26 (s, 9H). LCMS: (FA) ES+470.2, ES−472.9

Provenance & Evidence