2-Methyl-3-butyn-2-ol → HCID 68667918, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 9-bromo-5-{[2,6-dichloro-4-(1-hydroxyethyl)phenyl]amino}benzo[c]-2,6-naphthyridin-1(2H)-one (292 mg, 0.61 mmol) in DMF (3 mL) were added triethylamine (0.255 mL, 1.83 mmol), copper iodide (23 mg, 0.12 mmol), tetrakis(triphenylphosphine)palladium (0) (70 mg, 0.06 mmol), and 2-methyl-3-butyn-2-ol (0.179 mL, 1.83 mmol). The solution was degassed by bubbling nitrogen gas and heated to 65° C. for 14 hr. The solution was diluted with EtOAc and washed with water, dried with Na2SO4, filtered, and concentrated under reduced pressure. Purification with column chromatography on silica gel (100% CH2Cl2 to 70% CH2Cl2/30% MeOH) provided 5-{[2,6-dichloro-4-(1-hydroxyethyl)phenyl]amino}-9-(3-hydroxy-3-methylbut-1-yn-1-yl)benzo[c]-2,6-naphthyridin-1(2H)-one as a mixture of enantiomers. The enantiomers were separated on Chiral Technology AD 2×25 cm column at 12 mL/min using 1:1 iPrOH/Heptane in a 25 min run. First enantiomer has a retention time of 7.57 min and the second enantiomer has a retention time of 15.74 min. For both enantiomers: 1H NMR (500 MHz, CD3OD) δ 9.80 (d, 1H), 7.60 (d, 1H), 7.50-7.40 (m, 3H), 7.34 (d, 1H), 3.90 (m, 1H), 1.48 (s, 3H), 1.47 (s, 3H), 1.12 (d, 3 H). LRMS (ESI) calc'd for C25H22Cl2N3O3 [M+H]+, 482.1; found 482.1.

Provenance & Evidence