Trifluoroacetic acid → N-(2-aminophenyl)-4-(3-cyano-5-{[(tetrahydro-2h-pyran-4-ylmethyl)amino]methyl}pyridin-2-yl)benzamide

Participants

Reaction Steps

N-(2-t-Butoxycarbonylaminophenyl)-4-(3-cyano-5-formylpyridin-2-yl)benzamide (0.20 g, 0.45 mmol; prepared as described in Method 15 below) and 4-aminomethyltetrahydropyridine (81 mg, 0.7 mmol) were dissolved in dichloromethane (6 ml). Titanium (IV) isopropoxide (0.27 ml, 0.9 mmol) was added and the mixture stirred at ambient temperature for 2 hours. Sodium borohydride (70 mg) and methanol (0.6 ml) were then added and the mixture stirred for a further 16 hours. Water (4 ml) and a saturated aqueous sodium bicarbonate solution (2 ml) were added and stirred for 10 minutes. The product was extracted with dichloromethane (3×10 ml) and the organic residues concentrated. The residue was purified using chromatography eluting with 10% methanol in ethyl acetate, and concentration of the solvent gave product as a gum. This was dissolved in dichloromethane (6 ml), trifluoroacetic acid (1.2 ml) added and the solution then stirred at ambient temperature for 2 hours. The resulting solution was absorbed onto an SCX-2 column, which was washed with methanol (3 column volumes) and then the product eluted with a 2M solution of ammonia in methanol (3 column volumes) then concentrated to give the product as a gum. This was re-precipitated by stirring in diethyl ether (3 ml) to give the title compound as a foam (73 mg, 37%). NMR Spectrum: (DMSO-d6) 1.18 (m, 2H), 1.66 (m, 3H), 2.46 (d, 2H), 3.29 (m, 2H), 3.85 (m, 4H), 4.95 (s, 2H), 6.62 (m, 1H), 6.80 (d, 1H), 7.00 (m, 1H), 7.21 (d, 1H), 8.00 (d, 2H), 8.16 (d, 2H), 8.39 (s, 1H), 8.39 (s, 1H), 9.78 (s, 1H); Mass Spectrum: M+H+ 442.

Provenance & Evidence