Reaction Steps
An ice cold solution of ethyl 4-(8-chloro-5-methylchroman-6-yl)-2,9-dimethyl-9H-pyrido[2,3-b]indole-3-carboxylate (262 mg, 0.584 mmol) in tetrahydrofuran (THF) (5 mL) was treated slowly with LAH (1M in THF) (1.751 mL, 1.751 mmol), and then stirred at rt for 18 hours. The reaction was treated with additional LAH (2×1 mL every two hours), cooled to 0° C., quenched slowly with 163 uL H2O, followed by 163 uL 15% aq. NaOH and 3×163 uL H2O. The mixture was stirred at rt for 2 hours, filtered, washed with EtOAc, and then concentrated to afford mixture of chlorinated and dechlorinated alcohol. The intermediate was dissolved in methanol (5.8 mL), treated with Et3N (0.325 mL, 2.334 mmol), formic acid (0.090 mL, 2.334 mmol), Pd/C (62.1 mg, 0.058 mmol), and stirred at 60° C. for 1 hour. The reaction was treated with additional Pd/C (small scoop) and heated overnight at 60° C. Added MeOH (2 mL), Et3N (330 uL), Pd/C (69 mg), formic acid (100 uL), stirred for 1 hour, added Pd/C (70 mg), and stirred for another hour until no starting material remained. The mixture was filtered through Celite™, washed with EtOAc, DCM, and MeOH, and then concentrated. Purification with column chromatography (0-100% EtOAc/hexane) gave (2,9-dimethyl-4-(5-methylchroman-6-yl)-9H-pyrido[2,3-b]indol-3-yl)methanol (170 mg, 0.456 mmol, 78% yield) as pale yellow oil. The intermediate was suspended in dichloromethane (DCM) (5.00 mL), treated with PCC (189 mg, 0.875 mmol), and stirred at rt for 2 hours. The mixture was diluted with DCM, filtered through Celite™, washed with EtOAc, and then concentrated. Purification by column chromatography (0-100% EtOAc/hexane) gave 2,9-dimethyl-4-(5-methylchroman-6-yl)-9H-pyrido[2,3-b]indole-3-carbaldehyde (122.5 mg, 0.331 mmol, 56.7% yield) as pale yellow solid: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 10.01 (s, 1 H), 7.50-7.40 (m, 2 H), 7.06 (ddd, J=2.2, 6.0, 8.0 Hz, 1H), 7.01 (d, J=8.3 Hz, 1 H), 6.85 (t, J=8.4 Hz, 2 H), 4.36-4.21 (m, 2 H), 4.01 (s, 3 H), 3.05 (s, 3 H), 2.81-2.69 (m, 2 H), 2.27-2.07 (m, 2 H), 1.89 (s, 3 H); LCMS (m/z) ES+=371 (M+1).
