p-Toluenesulfonic acid → N-((6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)-7-methoxy-1,5-naphthyridin-4-amine

Participants

Reaction Conditions

Reaction Steps

In a 250 mL round bottom flask under N2 were dissolved HATU (1762 mg, 4635 μmol), 1-(6-chloropyridazin-3-yl)hydrazine (536 mg, 3708 mol), 2-(7-methoxy-1,5-naphthyridin-4-ylamino)acetic acid hydrochloride (1.00 g, 3708 μmol) in 25 mL of MeCN then stirred and cooled down at −40° C. then treated with TRIETHYLAMINE (2584 μl, 18540 μmol) and warmed to rt. After 30 min the reaction mixture based on LC-MS was evaporated under reduced pressure and dry under high vacuum. The crude solid was dissolved in 100 mL of i-PrOH then treated with Ts-OH (2821 mg, 14832 μmol) and heated at 80° C. After 3 h the reaction mixture based on LC-MS was diluted with DCM then neutralized with NaOH (1N). The aqueous phase was extracted 3× with DCM with 10% MeOH then the organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The crude mixture was triturated with hot i-PrOH then cooled down and filtered (662 mg) and the mother liquor was evaporated under reduced pressure and purified by MPLC (ISCO) (210 mg) with DCM:MeOH 100:0 to 90:10 to afforded in combined yields N-((6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)-7-methoxy-1,5-naphthyridin-4-amine (872 mg, 69% yield) as a off-white solid. MS m/z=342.1 [M+1]+. Calc'd for C15H12ClN7O: 341.7.

Provenance & Evidence