Acetic Acid → HCID 117926313, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of methyl 2-picolinoyl nicotinate, compound 6, (130 mg, 0.54 mmol), benzylhydrazine dihydrochloride (146 mg, 0.81 mmol), diisopropylethylamine (104 mg, 0.81 mmol), and ethanol (5 mL) was heated overnight at 75° C. To the reaction mixture was added acetic acid (46 μL, 0.81 mmol). The reaction mixture was heated at 75° C. for 2 h and then 100° C. for 2 h. After cooling the excess solvent was removed under reduced pressure. The residue was partitioned between 15 mL of ethyl acetate and 10% aqueous sodium carbonate. The aqueous fraction was further extracted with 2×15 mL of ethyl acetate. The organic extracts were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by normal phase flash chromatography eluting with 0-5% methanol in dichloromethane over 20 minutes. Like fractions containing product were combined and concentrated under reduced pressure to give 6-benzyl-8-(pyridin-2-yl)pyrido[2,3-d]pyridazin-5(6H)-one, RL-10 (44 mg, 0.13 mmol). 1H NMR (400 MHz, Chloroform-d) δ 9.11 (dd, J=4.5, 1.8 Hz, 2H), 8.89 (d, J=3.9 Hz, 2H), 8.77 (dd, J=8.1, 1.8 Hz, 1H), 7.91 (s, 2H), 7.68 (dd, J=8.1, 4.5 Hz, 1H), 7.49 (dd, J=25.2, 5.7 Hz, 3H), 7.37-7.24 (m, 5H), 5.53 (s, 2H). LCMS: (M+H)+, 316.

Provenance & Evidence