Sodium hydride → 2-[4-(4-Acetyl-piperazin-1-ylmethyl)-3-methyl-pyridin-2-ylamino]-thiazole-5-carbonitrile

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Reaction Steps

NaH (60% dispersion, 14 mg, 0.35 mmol) was stirred in 1 ML anhydrous THF. 1-[4-(2-Amino-3-methyl-pyridin-4-ylmethyl)-piperazin-1-yl]-ethanone (0.039 g, 0.157 mmol) was added followed, after 10 min by the addition of 2-chloro-thiazole-5-carbonitrile (0.027 g, 0.19 mmol). The reaction was stirred at RT for 30 min then was heated to reflux. After 2 h an additional 0.010 g NaH (0.25 mmol) was added. After 1 h the reaction was cooled to RT and quenched with water. The pH was adjusted to 7 with 1M HCl and the mixture was extracted 3× with EtOAc. The combined organic phases were dried over Na2SO4, filtered and concentrated. The residue was purified by reverse phase HPLC to provide the pure titled compound. TFA salt: 1H NMR (CD3OD) δ 8.37 (d, 1H, J=5.1 Hz), 8.08 (s, 1H), 7.19 (d, 1H, J=5.1 Hz), 4.45 (s, 2H), 3.81 (bs, 4H), 3.35 (s, 4H), 2.47 (s, 3H), 2.15 (s, 3H). MS [M+H]+=357.

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