Lithium Hydroxide → N-{2-[(6-{[5-(2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-3-(hydroxymethyl)pyridin-4-yl)-1-methyl-2-oxo-1,2-dihydropyridin-3-yl]amino}pyridin-2-yl)oxy]ethyl}prop-2-enamide

Participants

Reaction Steps

—Step 6: To a solution of 101f (257 mg, 0.387 mmol) in THF/i-PrOH/H2O (5.0/3.0/2.0 mL) was added LiOH (46 mg, 1.95 mmol) at room temperature. The reaction was stirred for 1 h. The mixture was diluted with water (15 mL) and extracted with DCM (15 mL×3). The combined organic layer was washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue solid was purified by reverse-phase prep-HPLC to afford 101 (95 mg, 39% two steps) as a white solid. MS-ESI: [M+H]+ 624.2. 1H NMR (500 MHz, CDCl3) δ 8.74 (d, J=2.0 Hz, 1H), 8.53 (d, J=5.0 Hz, 1H), 9.70 (s, 1H), 7.73 (d, J=2.0 Hz, 1H), 7.50-7.48 (m, 1H), 7.29-7.27 (m, 1H), 6.85 (s, 1H), 6.46-6.44 (m, 2H), 6.27-6.23 (m, 2H), 6.05-6.00 (m, 1H), 5.61-5.59 (m, 1H), 4.98-4.96 (m, 1H), 4.72-4.70 (m, 1H), 4.55-4.53 (m, 1H), 4.39-4.29 (m, 3H), 4.19-4.16 (m, 2H), 3.96-3.94 (m, 1H), 375-3.73 (m, 4H, overlap), 3.64-3.60 (m, 1H), 2.61-2.59 (m, 2H), 2.53-2.51 (m, 2H), 1.30 (s, 6H).

Provenance & Evidence