Reaction Steps
A mixture of 5-(4-chloro-6-oxo-6,7-dihydro-pyrrolo[2,3-d]pyrimidin-5-ylidenemethyl)-4-methyl-1H-pyrrole-2-carboxylic acid (2-morpholin-4-yl-ethyl)-amide (44 mg, 0.11 mmol), 3-chloro-4-fluoro-phenylamine (154 mg, 1.1 mmol) and p-toluenesulfonic acid monohydrate (10.1 mg, 0.053 mmol), 1-methyl-2-pyrrolidinone (2.5 mL) and 2-methoxyethyl ether (2.5 ml) was heated to 190° C. for 16 hours and concentrated. The residue was purified by reverse phase HPLC, then dissolved in 2N HCl and acetonitrile and freeze-dried to give 24 mg (39%) of 5-[4-(3-chloro-4-fluoro-phenylamino)-6-oxo-6,7-dihydro-pyrrolo[2,3-d]pyrimidin-5-ylidenemethyl]-4-methyl-1H-pyrrole-2-carboxylic acid (2-morpholin-4-yl-ethyl)-amide hydrochloride as a red solid. 1H NMR (360 MHz, DMSO-d6) δ 13.46 (s, 1H, NH), 11.79 (s, 1H, NH), 10.74 (br s, 1H, HCl), 9.33 (s, 1H), 8.83 (t, J=5.5 Hz, 1H, NH), 8.33 (s, 1H, H-vinyl), 7.74 (dd, J=2.39, 6.68 Hz, 1H), 7.38-7.47 (m, 2H), 7.35 (t, J=9.03, 1H), 6.94 (s, br, 1H), 3.96 (dt, J=5.74, 11.37 Hz, 2H, CH2), 3.80 (t, J=12.10 Hz, 2H, CH2), 3.68 (dd, J=5.99 & 11.61 Hz, 2H, CH2), 3.52 (d, br, J=12.44 Hz, 2H, CH2), 3.29-3.31 (m, 2H, CH2), 3.10-3.13 (m, 2H, CH2), and 2.23 (s, 3H, CH3). MS 526 [M+].
