Yield: 90%

Reaction Conditions:

Stage #1:N-(4-(3-chloro-2-(diphenylmethyleneamino)pyridin-4-yloxy)-3-fluorophenyl)-5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxamide with hydrogenchloride;water in tetrahydrofuran at 20; for 1 h;
Stage #2: with sodium hydrogencarbonate in waterCooling;

Steps:

1
To a solution of N-(4-(3-chloro-2-(diphenylmethyleneamino)pyridin-4- yloxy)-3-fluorophenyl)-5-(4-fluorophenyl)-4-oxo-l,4-dihydropyridine-3-carboxamide (410 mg, 0.65 mmol) in THF (10 mL) at room temperature was added aqueous HCl (2 M, 0.81 mL, 1.62 mmol). The reaction mixture was stirred at room temperature for 1 h and then concentrated in vacuo. Cold 5% aq. νaHCθ3 (5 mL) was then added to the residue. The solid that formed was collected by filtration, washed with water and then ether, and dried under vacuum to give the desired product (275 mg, 90%). ¹H NMR (DMSO-(Z₆) δ 13.31 (s, 1 H), 12.70 (br s, 1 H), 8.63 (d, 1 H, J= 1.30 Hz), 8.09 (d, 1 H, J= 1.50 Hz), 8.02 (dd, I H, J= 2.50, 13.10 Hz), 7.76 (d, 1 H, J= 5.50 Hz), 7.71 (m, 2 H), 7.44 (dd, 1 H, J= 1.50, 8.80 Hz), 7.31 (t, 1 H, J= 8.80 Hz), 7.27 (t, 2 H, J= 8.80 Hz), 6.43 (br s, 2 H), 5.96 (d, 1 H, J= 5.60 Hz); MS(ESI⁺) m/z 469 (M + H)⁺.

References:

BRISTOL-MYERS SQUIBB COMPANY WO2009/94417, 2009, A1 Location in patent:Page/Page column 27; 37