Hydrochloric Acid → 3-Chloro-6-(2-propyl-thiazol-5-yl)-pyridazine

Participants

Reaction Conditions

Reaction Steps

N-butyllithium (2.5M in Hexanes, 1.3 mL, 3.3 mmol) was added dropwise over 2 min to a −78° C. solution of 2-propylthiazole (380 mg, 3 mmol) in THF (8 mL). After stirring for 45 min at −78° C., a solution of zinc chloride (0.5M in THF, 7 ML, 3.5 mmol) was added. The solution was stirred for 1 h, during which it warmed to rt. Tetrakis-triphenylphosphine (172 mg, 0.15 mmol) and 3,6-dichloropyridazine were added and the reaction was heated to 68° C. for 16 h. After cooling to rt, methanol (3 mL) and 2N HCl (2 mL) were added. The pH was adjusted to ˜8 with Na2CO3 and the mixture was partitioned between EtOAc (50 mL) and water (30 mL). The organic layer was washed with water (2×10 mL) and brine (20 mL) and was dried over Na2SO4. Concentration of the solution in vacuo followed by SiO2 flash chromatography yielded the product as an off-white solid (200 mg, 28%). 1H-NMR (CDCl3): δ 8.16 (1H, s), 7.77 (1H, d, J=8.8 Hz), 7.53 (1H, d, J=8.8 Hz), 3.04 (2H, t, J=7.6 Hz), 1.89 (2H, sextet, J=7.6 Hz), 1.06 (2H, t, J=7.6 Hz). ESI-MS (m/z): Calcd. for C10H10ClN3S: 239.0/241.0; found: 240.2/242.2 (M+H; M+2+H).

Provenance & Evidence