Dimethylformamide → HCID 9936160, compound

Participants

Reaction Conditions

Reaction Steps

6-(2,5-Dichlorobenzyl)-1-hydroxy-2-[2-(4-morpholinyl)ethyl]-1,6-dihydropyrrolo[3′,4′:5,6]-pyrido[3,4-b]indol-3(2H)-one was prepared by a slight modification of a reported procedure (Dodd et al., J Org. Chem. 1993, 58:7587): A solution of 9-(2,5-dichlorobenzyl)-N-[2-(4-morpholinyl)ethyl]-9H-β-carboline-3-carboxamide (400 mg, 0.83 mmol) in anhydrous THF (12 mL) was stirred and cooled to −78° C. under nitrogen. When an internal temperature of −78° C. was attained, a 1.0 M methyllithium in diethyl ether/cumene solution (4.2 mL, 4.2 mmol) was added by syringe over a period of 0.3 hours. The reaction mixture developed a very dark blue color after complete addition of methyllithium. The solution was stirred at −78° C. for 2 hours, and the dry ice-acetone bath was then replaced with an ice-water bath. After 0.5 hour, anhydrous DMF (3070 mg, 4.2 mmol) was added dropwise, and the reaction mixture was stirred at room temperature for another 15 hours. The solution was cooled to 0° C., and distilled water was slowly added while maintaining the internal temperature of the reaction mixture at 0-5° C. The solution was concentrated to about 10 mL under reduced pressure, excess CH2Cl2 was added, and the mixture was washed with water. The organic phase was dried (Na2SO4), and the solvents were removed in vacuo. The resulting crude residue was washed several times with ether. Purification of the crude material by column chromatography on silica with 4% 2M MH3—CH3OH in CH2Cl2 as eluent furnished the lactam (106 mg, 25%) as a pale yellow solid. A 241 mg portion (60%) of unreacted starting material was recovered by evaporating combined ether layers and chromatography fractions. 1H NMR (CDCl3) δ8.76 (s, 1H), 8.48 (d, J=7.6 Hz, 1H), 7.66 (td, J=8.2 Hz, 0.91 Hz, I H), 7.46 (t,J=7.4 Hz, 1H), 7.35-7.40 (4-line multiplet, 2H), 7.18 (dd, J=8.5 Hz, 2.4 Hz, 1H), 6.42 (d,J=2.3 Hz, 1H), 6.17 (s, 1H), 5.56 (s, 2H), 4.46 (dt, J=9.6, 2.7 Hz, 1H), 3.83 (t, J=4.3 Hz, 4H), 3.47 (td,J=9.8, 1.5 Hz, 1H), 2.78-2.86 (m, 3H), 2.51-2.64 (m, 3H), 1.50-2.30 (v. br. s, 1H); MS (APCI; (M+H)+) m/z 511.

Provenance & Evidence