1-Hydroxybenzotriazole → N-(4-(2-Aminopyridin-4-yloxy)-3-fluorophenyl)-2-oxo-1-phenyl-1,2-dihydropyridine-3-carboxamide

Participants

Role	Name	HCID	Charge
Reactant	1-Hydroxybenzotriazole	HCID 75771	—
Reactant	1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride	HCID 2723939	—
Reactant	2-Oxo-1-phenyl-1,2-dihydropyridine-3-carboxylic acid	HCID 21081585	—
Reactant	N-(4-(6-(4-(Benzyloxy)phenylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-N3-(4-fluorophenyl)malonamide	HCID 59853038	—
Solvent	Dimethylformamide	HCID 6228	—
Product	N-(4-(2-Aminopyridin-4-yloxy)-3-fluorophenyl)-2-oxo-1-phenyl-1,2-dihydropyridine-3-carboxamide	HCID 46852003	45.2%

Reaction Steps

To a solution of 2-oxo-1-phenyl-1,2-dihydropyridine-3-carboxylic acid (36 mg, 0.17 mmol) and HOBt (18 mg) in DMF (3 mL) at rt was added EDCI.HCl (45 mg, 0.23 mmol) followed by 4-(4-amino-2-fluorophenoxy)pyridine-2-amine (Compound B of Example 24, 36 mg, 0.17 mmol), and the reaction mixture was stirred at rt overnight. Purification of the reaction mixture by preparative HPLC afforded the title compound (32 mg, 36%) as a beige colored solid (TFA salt). 1H NMR (DMSO-d6) δ 13.35 (br s, 1H), 12.11 (s, 1H), 8.52 (dd, 1H, J=7.3, 2.1 Hz), 8.08 (dd, 1H, J=6.6, 2.1 Hz), 8.03 (d, 1H, J=2.3 Hz), 7.89 (d, 1H, J=7.2 Hz), 7.81 (s, 1H), 7.54-7.36 (m, 6H), 6.69-6.63 (m, 2H), 6.08 (d, 1H, J=2.4 Hz), 3.55 (br s, 1H); MS(ESI+) m/z 417.2 (M+H)+.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07714138B2
Source dataset	uspto-grants-2010_05
ORD ID	ord-a36b55385906485aba1bfd95b37730d7
Source note	uspto-grants-2010_05