Hydrochloric Acid → 2-{4-[2-(Thiazolo[5,4-d]pyrimidin-7-ylamino)-ethyl]-phenoxy}-isonicotinonitrile

Participants

Reaction Steps

7-Chlorothiazolo[5,4-d]pyrimidine (0.26 g, 1.5 mmol), 2-[4-(2-aminoethyl)-phenoxy]-isonicotinonitrile (0.36 g, 1.5 mmol) and Et3N (231 mg, 2.3 mmol) were dissolved with magnetic stirring in DMF (10 mL) in a 25 mL round bottom flask equipped with a dry nitrogen line at 25° C. After stirring overnight, the reaction was diluted with H2O (100 mL) and neutralized with 2 N HCl. The mixture was partitioned into a 1:1 solution of EtOAc/Et2O (3×50 mL). The pooled organic fractions were filtered and concentrated in vacuo to afford a yellow gum, 0.54 g. The gum was dissolved in a small volume of EtOAc and passed through a short SiO2 column with EtOAc/Et2O eluent. The appropriate fractions were pooled and concentrated in vacuo to afford 2-{4-[2-(thiazolo[5,4-d]pyrimidin-7-ylamino)-ethyl]-phenoxy}-isonicotinonitrile (Compound 2; 230 mg) as a white solid: mp 145-148° C.; 1H NMR (400 MHz, CDCl3) δ 8.77 (s, 1H), 8.55 (s, 1H), 8.33 (dd, J=5.1, 0.7 Hz, 1H), 7.39-7.29 (m, 2H), 7.20 (dd, J=5.1, 1.3 Hz, 1H), 7.17-7.13 (m, 1H), 7.13-7.06 (m, 2H), 6.27 (s, 1H), 3.95 (dd, J=12.6, 6.2 Hz, 2H), 3.05 (t, J=7.1 Hz, 2H); ESIMS m/z 375.2 ([M+H]+).

Provenance & Evidence