1-Hydroxybenzotriazole → N-{4-[2-Amino-5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl]phenyl}-5-(4-fluorophenyl)-4-oxo-1-(2,2,2-trifluoroethyl)-1,4-dihydropyridine-3-carboxamide

Participants

Role	Name	HCID	Charge
Reactant	1-Hydroxybenzotriazole	HCID 75771	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 9886157	—
Reactant	5-(4-Fluorophenyl)-4-oxo-1-(2,2,2-trifluoroethyl)-1,4-dihydropyridine-3-carboxylic acid	HCID 86700050	—
Reactant	3-(4-Aminophenyl)-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine	HCID 86700064	—
Catalyst	4-(Dimethylamino)pyridine	HCID 14284	—
Solvent	Water	HCID 962	—
Solvent	Dimethylformamide	HCID 6228	—
Product	N-{4-[2-Amino-5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl]phenyl}-5-(4-fluorophenyl)-4-oxo-1-(2,2,2-trifluoroethyl)-1,4-dihydropyridine-3-carboxamide	HCID 86700065	30.2%

Reaction Steps

HOBt (51 mg), HATU (215 mg), DMAP (23 mg) and DIPEA (131 μl) were added to a solution of the Compound obtained in Step 2 of Example 9 (131 mg) in DMF (2 ml) at room temperature. The reaction mixture was stirred at room temperature for 1.5 hours. The compound obtained in Step 1 of Example 47 (100 mg) was added to the reaction mixture at room temperature. The reaction mixture was stirred at 50° C. for 1.5 hours and returned to room temperature. Water was added to the reaction mixture, and the precipitated solid was collected by filtration. The resulting solid was purified by PLC [dichloromethane:methanol=15:1 (v/v)] to give 64 mg of the title compound as a solid.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08933103B2
Source dataset	uspto-grants-2015_01
ORD ID	ord-5cff4277cd064f038b33257ed1383555
Source note	uspto-grants-2015_01