Sodium hydride → HCID 18506868, compound

Participants

Reaction Steps

tert-Butyl 4-[1-(4-acetylpiperazin-1-yl)ethyl]pyridin-2-ylcarbamate (16-4, 137 mg, 0.39 mmole) was taken up in 4 M HCl in dioxane (10 mL) at RT. After 60 hr the mixture was diluted with H2O and neutralized with solid NaHCO3. The resulting mixture was extracted with CH2Cl2 (3×). The combined organic layers were dried (MgSO4), filtered, and concentrated. The residue was taken up in dry THF (2 mL). To this was added NaH (40 mg, 60% dispersion in mineral oil, 0.98 mmole). After gas evolution had ceased 2-chloro-5-cyano-1,3-thiazole (85 mg, 0.59 mmole) was added and the mixture heated to reflux. After 3 hr the mixture was cooled to RT and quenched with saturated NH4Cl. The layers were separated and the aqueous layer extracted with EtOAc (4×). The combined organic layers were dried (MgSO4), filtered, and concentrated. Flash column chromatography (gradient, 0-15% EtOH/EtOAc) gave the titled compound as a tan solid. 1H-NMR (500 MHz, d6-DMSO) δ 12.18 (s, 1 H), 8.34 (d, 1 H, J=5.13 Hz), 8.26 (s, 1 H), 7.12 (s, 1 H), 7.05 (d, 1 H, J=5.13 Hz), 3.52-3.41 (m, 5 H), 2.44-2.03 (m, 4 H), 1.96 (m, 3 H), 1.28 (d, 3 H, J=6.59 Hz); MS (ES) (M+H)+ 357.

Provenance & Evidence