N-(2-t-Butoxycarbonylaminophenyl)-4-(3-cyano-5-formylpyridin-2-yl)benzamide (0.80 g, 1.8 mmol; prepared as described in Method 15 below) and ethylamine (1.4 ml of a 1.0M solution in THF, 1.4 mmol) were dissolved in dichloromethane (15 ml). Titanium (IV) isopropoxide (1.55 g, 1.62 ml, 5.4 mmol) was added and the mixture stirred at ambient temperature for 1 hour. Sodium borohydride (342 mg) and methanol (3 ml) were then added and the mixture stirred for a further 30 minutes. Water (20 ml) then a saturated aqueous sodium bicarbonate solution (30 ml) was added and the product extracted with dichloromethane (3×30 ml). The organic residues were concentrated and the residue purified using flash column chromatography eluting with ethyl acetate, followed by 2M NH3/MeOH (3-5%) in ethyl acetate to give t-butyl {2-[(4-{3-cyano-5-[(ethylamino)methyl]pyridin-2-yl}benzoyl)amino]phenyl}carbamate (508 mg) as a white solid. This was dissolved in methanol (4 ml), a 4M solution of hydrogen chloride in 1,4-dioxan (10 ml, 40 mmol) was added and the solution then stirred at ambient temperature for 2 hours. The solvent was evaporated, methanol (5 ml) was added and the resulting solution was absorbed onto an SCX-2 column, which was washed with methanol (2 column volumes) and then eluted with a 2M solution of ammonia in methanol (2 column volumes) to give the product as a foam. This was re-precipitated by stirring in diethyl ether (20 ml) to give the title compound as a white solid (359 mg, 53%); NMR Spectrum: (DMSO-d6 373K) 1.08 (t, 3H), 2.62 (q, 2H), 3.67 (s, 2H), 4.73 (br s, 2H), 6.63 (m, 1H), 6.82 (m, 1H), 6.98 (m, 1H), 7.27 (m, 1H), 7.99 (d, 2H), 8.13 (d, 2H), 8.28 (d, 1H), 8.88 (d, 1H), 9.50 (br s, 1H); Mass Spectrum: M+H+ 372.
