Formaldehyde → 6-tert-butyl-8-fluoro-2-(2-hydroxymethyl-3-{1-methyl-5-[5-(6-methyl-2,6-diaza-spiro[3.3]hept-2-yl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridazin-3-yl}-phenyl)-2H-phthalazin-1-one

Participants

Reaction Conditions

Reaction Steps

In a 25 mL round-bottomed flask, 2-(3-(5-(5-(2,6-diazaspiro[3.3]heptan-2-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)-2-(hydroxymethyl)phenyl)-6-tert-butyl-8-fluorophthalazin-1(2H)-one (146 mg, 234 μmol), 30% formaldehyde (42.2 mg, 38.8 μl, 1.41 mmol) and sodium cyanoborohydride (177 mg, 2.81 mmol) were combined with methanol (9 ml) to give an orange solution. The reaction mixture was stirred at 25° C. for 4 h. The crude reaction mixture was concentrated in vacuo, diluted with 10 mL 0.1 M NaOH and extracted with DCM (3×15 mL). The organic layers were dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 40 g, 0% to 10% MeOH in DCM). The light yellow powder was dried under vacuum at 25° C. for 3 hrs to give 0.33 g (22%) of the title compound. (M+H)+=637 m/e. 1H NMR (300 MHz, CHLOROFORM-d) δ: 8.37 (s, 1H), 8.28 (d, J=2.3 Hz, 1H), 8.13 (s, 1H), 7.38-7.71 (m, 6H), 6.75-6.93 (m, 2H), 4.40 (s, 2H), 3.96 (s, 4H), 3.88 (s, 3H), 3.47 (s, 4H), 2.37 (s, 3H), 1.42 (s, 9H).

Provenance & Evidence