Sodium borohydride → 6-tert-Butyl-2-(3-(5-(5-((2S,5R)-2,5-dimethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-5-fluoro-2-(hydroxymethyl)phenyl)-8-fluorophthalazin-1(2H)-one

Participants

Reaction Steps

At 0° C., to a solution of 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(5-(5-((2S,5R)-2,5-dimethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-4-fluorobenzaldehyde 108a (54 mg, 0.076 mmol) in methanol (5 mL) was added sodium borohydride (9.0 mg, 0.23 mmol). The mixture was stirred for 60 minutes. It was then quenched with water (1.0 mL) and concentrated under reduced pressure. The residue was purified by reverse-phase prep-HPLC to afford 108 (12 mg, 22%). MS: [M+H]+ 712.3. 1H NMR (500 MHz, CDCl3) δ 8.63 (d, J=2.5 Hz, 1H), 8.31 (d, J=2.0 Hz, 1H), 8.05 (d, J=2.5 Hz, 1H), 7.87 (s, 1H), 7.58-7.55 (m, 2H), 7.44 (d, J=2.0 Hz, 1H), 7.36 (s, 1H), 7.30 (d, J=2.0 Hz, 1H), 7.12 (dd, J=2.5, 8.5 Hz, 1H), 6.82 (d, J=8.5 Hz, 1H), 4.76-4.73 (m, 2H), 4.68-4.61 (m, 2H), 4.38-4.36 (m, 2H), 3.74-3.72 (m, 2H), 3.72 (s, 3H), 3.22-3.20 (m, 1H), 2.94-2.92 (m, 1H), 2.74-2.72 (m, 2H), 2.50-2.48 (m, 1H), 1.98-1.96 (m, 1H), 1.45 (s, 9H), 0.93-0.91 (m, 6H).

Provenance & Evidence