Reaction Steps
3-Amino-6-methyl-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione (3, 201 mg, 0.72 mmol) was dissolved in tetrahydrofuran (30 mL) and cooled to 0° C. Methyl oxalyl chloride (4, 0.1 mL, 1.16 mmol) and triethylamine (0.2 mL) were added dropwise and the reaction mixture was stirred for 2 h at 0° C. The reaction mixture was diluted with water (100 mL) and extracted with chloroform (4×50 mL). The solvent was removed under vacuum and the compound passed through a short silica gel column chromatography, eluting with chloroform-methanol, 9:1. The impure solid, compound 9, was dissolved in a solution of sodium hydroxide (0.1 g, 2.5 mmol) in ethanol (50 mL) and water (1 mL) and the reaction mixture was stirred overnight at room temperature. The solvent was removed under vacuum and the residue purified by silica gel column chromatography, eluting with chloroform-methanol-acetic acid, 90:9:1. Compound 14 was obtained as a reddish-brown solid (103 mg, 44.7%, after 2 steps): mp 360° C. (dec). IR (Film) 3325, 2928, 1692, 1657, 1600, 1580, 1533, 1435, 1319, 1197, 903, 701 cm−1; 1H NMR (300 MHz, DMSO-d6) δ 10.9 (s, 1 H), 8.70 (s, 1 H), 8.35 (d, J=8.2 Hz, 1 H), 8.02 (s, 1 H), 7.90 (br s, 1 H), 7.45 (m, 3 H), 3.89 (s, 3 H); 13C NMR (125 MHz, DMSO-d6) δ 190.1, 162.4, 162.2, 157.9, 156.3, 137.5, 136.9, 134.6, 134.0, 131.4, 128.4, 126.9, 124.4, 123.5, 123.4, 122.8, 118.5, 106.9; ESIMS m/z (rel intensity) 347 [(M-H+)−]; negative ion; HRESIMS calcd for C19H12N2O5 347.0668 [(M-H+)−], found 347.0664 [(M-H+)−]; HPLC purity: 95.2% (MeOH—H2O, 85:15), 95.7% (MeOH—H2O, 75:25).
