Pentylamine → 6-Chloropyridazine-3-carboxylic acid methylpentyl amide

Participants

Reaction Steps

To a mixture of 6-oxo-1,6-dihydropyridazine-3-carboxylic acid monohydrate (3.50 g, 22.1 mmol) in chloroform (110 mL) was added thionyl chloride (8.1 mL, 110 mmol) then catalytic amount of DMF (0.6 mL). The reaction mixture was heated at reflux for 20 hours during this time reaction mixture turn to dark green. After cooling the solvent was removed in vacuo. The crude material was dried under high vacuum for 30 minutes. The residue dissolved in dichloromethane (110 mL) was added dropwise to a solution of amyl amine (3.84 mL, 33.1 mmol) and triethylamine (5.60 mL, 40.2 mmol) at 0° C. The reaction mixture was stirred at room temperature for 2 hours. The organic layer was washed with water, dried over Na2SO4, filtered, and concentrated. The crude material was purified by column chromatography eluting with ethyl acetate:hexane (4:1) to obtain 6-chloropyridazine-3-carboxylic acid methylpentyl amide (4.8 g, 99%). M.p. 98-101° C. 1H NMR (300 MHz, CDCl3) δ 8.28 (d, J=7.2 Hz, 1H), 8.05 (s, br., 1H), 7.68 (d, J=7.2 Hz, 1H), 3.51 (q, J=5.6 Hz, 2H), 1.69-1.63 (m, 2H), 0.90 (t, J=5.6 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 161.5, 158.9, 151.8, 129.4, 128.1, 39.8, 29.1, 29.1, 22.4, 14.0. MS (ES+) m/z 228 (M+1).

Provenance & Evidence