Morpholine → 3-(3-chloro-4-(2-morpholinoethoxy)phenyl)-7-morpholino-9H-carbazole-1-carboxamide

Participants

Reaction Conditions

Reaction Steps

3-(4-(2-Bromoethoxy)-3-chlorophenyl)-7-morpholino-9H-carbazole-1-carboxamide (110 mg, 0.146 mmol, Example 407A) was dissolved in DMF (5 ml). Morpholine (0.045 ml, 0.517 mmol) and K2CO3 (66 mg, 0.478 mmol) were added and the mixture heated to 75° C. for 1 hour. Additional morpholine (0.10 ml, 1.148 mmol) was added and the mixture heated for one additional hour. The mixture was concentrated to a volume of ˜1 ml, then diluted with 3 ml DMSO+3 ml MeOH, filtered through a 0.45 um Nylon filter and purified by prep HPLC. Product containing fractions were evaporated to dryness to give 67.8 mg 3-(3-chloro-4-(2-morpholinoethoxy)phenyl)-7-morpholino-9H-carbazole-1-carboxamide. MS (ESI) m/e+=535/537, m/e−=533/535 [1 Cl isotope pattern]. HPLC retention time 15.81 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), then isocratic at 100% B. 1H NMR (DMSO-d6) δ ppm 11.13 (s, 1H), 8.49 (d, 1H, J=1.5), 8.34 (b, 1H), 8.14 (d, 1H, J=1.5), 8.07 (d, 1H, J=8.5), 7.99 (d, 1H, J=2.3), 7.82 (dd, 1H, J=8.6, 2.4), 7.51 (b, 1H), 7.31 (d, 1H, J=8.8), 7.24 (d, 1H, J=2.0), 6.94 (dd, 1H, J=8.8, 2.0), 4.26 (t, 2H, J=5.8), 3.83-3.79 (m, 4H), 3.64-3.59 (m, 4H), 3.22-3.17 (m, 4H), 2.79 (t, 2H, J=5.8), 2.58-2.54 (m, 4H).

Provenance & Evidence