Reaction #434738

Reaction equation

4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)-3-fluorobenzenamine

1-(3-Fluoro-4-(5-methyl-6-(2-(4-methylpiperazin-1-yl)ethoxy)pyrrolo[2,1-f][1,2,4] triazin-4-yloxy)phenyl)-3-(2-(4-fluorophenyl)acetyl)thiourea, bis-hydrochloride salt

Compound B

1-(3-Fluoro-4-(5-methyl-6-(2-(4-methylpiperazin-1-yl)ethoxy)pyrrolo[2,1-f][1,2,4] triazin-4-yloxy)phenyl)-3-(2-(4-fluorophenyl)acetyl)thiourea, bis-hydrochloride salt

2-hydroxynicotinic acid

HATU

DIPEA

→

desired product

Yield 22.0%

N-(4-(1H-Pyrrolo[2,3-b]pyridin-4-yloxy)-3-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide

Yield 22.0%

Solvents

DMF

Conditions

Workup

1. 1
   Concentrationconcentrated in vacuo
2. 2
   OtherThe residue was was purified by preparative HPLC

Procedure

To a stirred solution of 4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)-3-fluorobenzenamine (24 mg, 0.1 mmol, Compound B of Example 132), 2-hydroxynicotinic acid (27 mg, 0.2 mmol), and HATU (76 mg, 0.2 mmol) in DMF (1 mL) was added DIPEA (0.1 mL) and DMAP (5 mg). The resulting mixture was stirred at rt for 2 h and concentrated in vacuo. The residue was was purified by preparative HPLC to give the desired product (8 mg, 22%) as a white solid. LC/MS(ESI+) m/z 365 (M+H)+.

Source