Acetic Acid → 3-(3-chloro-4-hydroxyphenyl)-7-morpholino-9H-carbazole-1-carboxamide

Participants

Reaction Steps

7-Amino-3-(3-chloro-4-hydroxyphenyl)-9H-carbazole-1-carboxamide (700 mg, 1.094 mmol, Example 406A) and sodium cyanoborohydride (400 mg, 6.37 mmol) were dissolved in methanol (20 mL)+THF (20.00 ml). Trimethyl orthoformate (10 ml, 90 mmol) and acetic acid (100 μl, 1.747 mmol) were added, followed by 28 ml of the crude reaction mixture from Example 406B (contained ˜4 mmol of 2,2′-oxydiacetaldehyde in CH2Cl2). The reaction mixture was stirred at room temperature for 90 minutes, then filtered through a Waters MCX cartridge (18 g adsorbent). The cartridge was washed with water, methanol and dichloromethane, then the product was eluted with 2M NH3 in MeOH. Evaporation of volatiles and purification by prep HPLC gave 149.0 mg 3-(3-chloro-4-hydroxyphenyl)-7-morpholino-9H-carbazole-1-carboxamide. MS (ESI) m/e+=422/424, m/e−=420/422 [1 Cl isotope pattern]. HPLC retention time 7.34 min. (Sunfire C18 3.5 μm, 3.0×150 mm column, 15 min gradient, 10-100% B, 0.5 mL/min. Solvent A: 5% CH3CN—95% H2O—0.1% TFA; Solvent B: 95% CH3CN—5% H2O—0.1% TFA). 1H NMR (DMSO-d6) δ ppm 11.13 (s, 1H), 10.22 (b, 1H), 8.45 (d, 1H, J=1.5), 8.32 (b, 1H), 8.11 (d, 1H, J=1.7), 8.07 (d, 1H, J=8.8), 7.89 (d, 1H, J=2.3), 7.67 (dd, 1H, J=8.5, 2.3), 7.50 (b, 1H), 7.27 (d, 1H, J=1.0), 7.09 (d, 1H, J=8.5), 6.97 (dd, 1H, J=8.7, 1.7), 3.86-3.79 (m, 4H), 3.25-3.19 (m, 4H).

Provenance & Evidence