2-Aminothiazole → 2-(6-Hydroxymethyl-pyridin-2-ylamino)-thiazole-5-carbonitrile

Participants

Reaction Conditions

Reaction Steps

An oven dried flask was charged with 6-(tert-butyl-dimethyl-silanyloxymethyl)-pyridin-2-ylamine (1.27 g, 5.33 mmol) and 10 ml anhydrous THF. The solution was cooled to 0° C. and NaH (60% dispersion, 0.43 g, 11 mmol) was added. The reaction was warmed to room temperature and 2-chloro-thiazole-5-carbonitrile (0.924 g, 6.39 mmol) was added. The reaction was heated to 50° C. for 4 h. An additional 0.200 g (1.38 mmol) 2-chloro-thiazole-5-carbonitrile was added and the reaction was heated overnight. After a total of 18 h the reaction was cooled and quenched with water. The pH was adjusted to 7 with 1M HCl. The resulting precipitate was filtered and washed with water. Purification in two batches by flash column chromatography (suspended material on 5 g silica, eluted DCM to 97:3 DCM/MeOH) afforded a mixture of the aminothiazole and starting aminopyridine. This aminothiazole (0.710 g, 2.05 mmol) was dissolved in 10 mL anhydrous THF and the resulting solution was cooled to 0° C. HF-pyr, 2.4 mL, was added and the reaction was allowed to warm to room temperature. After 1 h the reaction was quenched by the addition of sat NaHCO3 (aq) and the THF was removed in vacuo. The resulting precipitate was filtered and washed with water to provide the titled compound. 1H NMR (DMSO-d6) δ 12.18 (s, 1H), 8.22 (s, 1H), 7.78 (t, 1H, J=7.6 Hz), 7.10 (d, 1H, J=7.5 Hz), 6.96 (d, 1H, J=8.2 Hz), 5.45 (t, 1H, J=5.7 Hz), 4.59 (d, 2H, J=5.9 Hz).

Provenance & Evidence