4-Fluoroaniline → N-(4-(1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

Participants

Reaction Steps

To a stirred mixture of 4-(1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorobenzenamine (73 mg, 0.20 mmol; obtained from Example 1, Step D) and ((4-fluorophenyl)carbamoyl)cyclopropanecarboxylic acid (49 mg, 0.220 mmol; prepared from cyclopropane-1,1-dicarboxylic acid and 4-fluoroaniline using the methods of WO 2005/030140 and by Shih and Rankin, Synth. Comm. 1996, 26(4), 833-836) in DMA (2 mL) was added N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (EDCI) (77 mg, 0.400 mmol). The reaction was stirred for 1 hour at room temperature. The reaction was diluted with EtOAc (10 mL) and water (10 mL). The phases were separated, and the organic phase washed with water (3×10 mL), brine (10 mL), dried (Na2SO4), filtered, and concentrated in vacuo. The crude was purified by preparative TLC eluting with 3% MeOH/DCM. The product was obtained as a waxy solid (42 mg, 33%). 1H NMR (400 MHz, CDCl3) δ 9.97 (s, 1H), 8.36 (d, J=5 Hz, 1H), 8.20 (s, 1H), 7.77 (m, 2H), 7.46 (m, 2H), 7.26 (m, 4H), 7.06 (m, 2H), 6.83 (d, J=9 Hz, 2H), 6.40 (d, J=5 Hz, 1H), 5.62 (s, 2H), 3.76 (s, 3H), 1.79 (m, 2H), 1.62 (m, 2H, overlaps with water).

Provenance & Evidence