Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → (R)-N-(4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl)-1-(2-hydroxypropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorobenzenamine (5.0 g, 0.016 mol) and (R)-1-(2-hydroxypropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid (6.2 g, 0.022 mol) in CH2Cl2 (100 mL) at 0° C. was added TEA (5.5 g, 0.054 mol), followed by HATU (10.3 g, 0.027 mol) in portions. The reaction mixture was stirred at 0° C. for 2 h, warmed up to rt and continued to stir overnight. The reaction mixture was washed with water (30 mL×3). The organic phase was dried over Na2SO4 and concentrated in vacuo. The residue was crystallized in a mixture of EtOAc/n-hexane (50 mL, v/v=5:1) to give the title compound as a pale yellow solid (7.8 g, 85.2%).

Provenance & Evidence