Hydrochloric Acid → methyl 3-{[(5-{4-[3-fluoro-4-({[(3-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-1H-pyrrol-3-yl)carbonyl]amino}propanoate

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Reaction Steps

A mixture of 5-{4-[3-fluoro-4-({[(3-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-1H-pyrrole-3-carboxylic acid (Example 75) (1.50 g, 3.36 mmol), HATU (1.41 g, 3.70 mmol) and N,N-diisopropylethylamine (1.29 g, 10 mmol) in anhydrous DMF (15 ml) was stirred at room temperature for 10 minutes, followed by addition of β-alanine methyl ester hydrochloride (558 mg, 4.0 mmol). The mixture was stirred for another 10 minutes and poured into 200 ml of water with vigorous stirring. 2M HCl was added dropwise until pH=4. The precipitates were filtered, washed with water and dried in vacuo to give the crude, which was purified by silica gel chromatography eluting with 3% of methanol in chloroform to give methyl 3-{[(5-{4-[3-fluoro-4-({[(3-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-1H-pyrrol-3-yl)carbonyl]amino}propanoate as off-white solid. Yield: 1.18 g, 66%.

Provenance & Evidence