Isatoic Anhydride → 7-(2-Methoxyethoxy)-4-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-9H-pyrido[3,4-b]indole-1-carboxamide

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-(3-amino-2-methylphenyl)-7-(2-methoxyethoxy)-9H-pyrido[3,4-b]indole-1-carboxamide (330 mg, 0.845 mmol), 1H-benzo[d][1,3]oxazine-2,4-dione (345 mg, 2.113 mmol), trimethoxymethane (0.926 mL, 8.45 mmol), and tris(nitrooxy)lanthanum, 6H2O (110 mg, 0.254 mmol) in tetrahydrofuran (Volume: 2 mL) was heated at 95° C. in a sealed vial for 20 hr. The mixture was diluted with ethyl acetate (100 mL), washed with water (30 mL), 1 N NaOH solution (30 mL), and brine (30 mL). The organic solution was dried over anhydrous MgSO4 and concentrated under vacuum. The residue was subjected to prep. reverse phase HPLC purification. The correct fractions were concentrated under vacuum, basified with saturated NaHCO3 solution, and extracted with ethyl acetate (3×35 mL). The combined extract was washed with brine (30 mL) and dried over anhydrous MgSO4. Removal of solvent under vacuum provided the desired product (188 mg, 0.362 mmol, 42.8% yield) as a yellow solid. The product is mixture of two atropisomers at rt. LCMS (M+H)+=520.29. 1H NMR (500 MHz, DMSO-d6) (recognizable peaks for the major atropisomer) δ: 11.68 (s, 1H), 8.44 (s, 1H), 8.21 (s, 1H), 7.36 (s, 1H), 7.25 (d, J=8.9 Hz), 4.17 (m, 2H), 3.73 (m, 2H), 3.35 (s, 3H), 1.81 (s, 3H).

Provenance & Evidence