Sodium Hydroxide → 6-tert-Butyl-8-fluoro-2-{2-hydroxymethyl-3-[1-methyl-5-(1'-methyl-1',2',3',4',5',6'-hexahydro-[3,4]bipyridinyl-6-ylamino)-6-oxo-1,6-dihydro-pyridazin-3-yl]-phenyl}-2H-phthalazin-1-one

Participants

Reaction Steps

2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(1-methyl-5-(5-(1-methylpiperidin-4-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate (1.6 g) was dissolved in 20 mL THF. To the reaction solution was added 12 mL of 2 N NaOH. The reaction mixture was stirred at room temperature overnight. Reaction was not complete. An additional 10 equiv. of 2 N NaOH was added and the reaction mixture was stirred at room temperature for an additional 2 hours. THF was added until the reaction mixture was homogeneous and the reaction was heated to 40° C. for 30 min. The reaction was allowed to cool to room temperature and stirred overnight. The reaction had gone to completion as indicated by LC/MS. The reaction was concentrated to a reduced volume to remove most of the THF. A solid formed which was collected by filtration. The solid was redissolved in DCM, filtered through pack of celite, washed with water, dried over Na2SO4, filtered and conc in vacuo. to afford the desired product as a white solid (1.27 g). (M+H)+=624 m/e. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.45 (s, 9H) 1.80-1.92 (m, 5H) 2.31-2.58 (m, 3H) 3.03 (d, J=8.28 Hz, 1H) 3.92 (s and overlapping multiplet, 4H) 4.45 (d, J=6.53 Hz, 2H) 6.93 (d, J=8.28 Hz, 1H) 7.45-7.63 (m, 5H) 7.65-7.71 (m, 1H) 8.22-8.32 (m, 3H) 8.61 (s, 1H).

Provenance & Evidence