Reaction Steps
A solution of 5-nitro-1H-indole-2-carboxylic acid ethyl ester (28) (750 mg, 3.20 mmol) in EtOAc (125 mL) was hydrogenated over Pd/C (10%, 300 mg) at 60 psi H2 for 5 h at room temperature. Then, the solid was removed by filtration through Celite, which was washed thoroughly with CH2Cl2 (400 mL) and MeOH (400 mL), and the filtrate was concentrated in vacuo. The residue was dissolved in DMF (30 mL) and the solution was cooled to 0° C. EDC.HCl (1.84 g, 9.60 mmol) and N,N-dimethylglycine hydrochloride (670 mg, 4.80 mmol) were added and the reaction mixture was allowed to warm to room temperature. After stirring for 21 h at this temperature, the solution was diluted with EtOAc (100 mL) and water (100 mL). The mixture was adjusted to pH 9 with a saturated aqueous solution of NaHCO3 and extracted with EtOAc (4×150 mL). The combined organic fractions were washed with water (4×200 mL) and brine (300 mL), dried (MgSO4), and the solvent was removed in vacuo. Purification by column chromatography (CH2Cl2/MeOH, 10:1) gave 29 (626 mg, 68% overall yield) as a pale brown solid. 1H NMR (200 MHz, CDCl3): δ=1.42 (t, J=7.1 Hz, 3 H, OCH2CH3), 2.40 (s, 6 H, NMe2), 3.11 (s, 2 H, 1′-H2), 4.41 (q, J=7.1 Hz, 2 H, OCH2CH3), 7.18 (d, J=1.8 Hz, 1 H, 3-H), 7.36 (d, J=8.8 Hz, 1 H, 7-H), 7.43 (dd, J=8.8, 1.8 Hz, 1 H, 6-H), 8.04 (sbr, 1 H, 4-H), 9.04 (sbr, 1 H, NH), 9.13 (sbr, 1 H, NH) ppm; 13C NMR (50.3 MHz, CDCl3): δ=14.3 (OCH2CH3), 46.0 (NMe2), 61.0 (OCH2CH3), 63.6 (C-1′), 108.5 (C-3), 112.2, 112.8 (C-4, C-7), 119.2 (C-6), 127.5, 128.2 (C-2, C-3a), 131.1 (C-5), 134.1 (C-7a), 162.0 (NHCO), 168.6 (CO2Et) ppm; MS (70 eV, EI): m/z (%)=289 (25) [M]+, 58 (100) [CH2NMe2]+; C15H19N3O3 (289.33): calcd. 289.1426, found 289.1426.
