Diisopropylethylamine → N-(4-(2-(4-methoxybenzylamino)pyridin-4-yloxy)-2-fluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

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Reaction Steps

1-((4-Fluorophenyl)carbamoyl)cyclopropanecarboxylic acid (see Example B1, 171 mg, 0.77 mmol), N-(4-methoxybenzyl)-4-(4-amino-3-fluorophenoxy)pyridin-2-amine (see PCT Publication No. WO 2008/046003, 200 mg, 0.59 mmol), TBTU (284 mg, 0.88 mol) and DIEA (0.12 ml, 0.73 mmol) were combined in DMF (1.5 mL) and the resultant mixture was stirred overnight. The reaction mixture was partitioned between saturated aqueous NaHCO3 (20 mL) and EtOAc (20 mL). The organic was washed with water (10 mL), brine (10 mL), and 5% aqueous lithium chloride solution (10 mL), and was then dried over MgSO4 and concentrated in vacuo. Dichloromethane was added to the residue and the resultant slurry was filtered. The collected precipitate was washed with CH2Cl2 and dried in vacuo to provide N-(4-(2-(4-methoxybenzylamino)pyridin-4-yloxy)-2-fluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (137 mg) as a white solid. The filtrate was concentrated and a second crop (46 mg, total yield 57%) was collected. MS (ESI) m/z: 545.1 (M+H+).

Provenance & Evidence