Hydrochloric Acid → HCID 66604099, compound

Participants

Reaction Steps

3-(3-Chloro-4-(morpholinomethyl)phenyl)-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamide (40.3 mg, 0.080 mmol, Example 399) was suspended in HCl (1 M solution in diethyl ether) (5 ml, 5.00 mmol) and sonicated briefly. (not completely dissolved. DCM was added (5 ml) in an unsuccessful attempt to dissolve more). The suspension was stirred at room temperature for 1 hour, then cooled to 0° C. Morpholine (5 ml, 57 4 mmol) was added, the ice bath removed and the mixture stirred at room temperature for 3 days. The reaction mixture was poured into a separating funnel that is loaded with EtOAc and sat. aq. NaHCO3 solution. Layers were separated, the aqueous extracted once more with EtOAc and the organic layer washed with brine, then dried over MgSO4, filtered and evaporated. The crude was purified by prep HPLC. Product containing fractions were filtered through a Waters MCX cartridge (1 g adsorbent), washed with MeOH and the product eluted with a 2M solution of NH3 in MeOH. Evaporation to dryness under a stream of nitrogen gave 10.8 mg white 3-(3-chloro-4-(morpholinomethyl)phenyl)-7-(2-morpholinopropan-2-yl)-9H-carbazole-1-carboxamide. MS (ESI) m/e−=545, m/e+=547 consistent with [M−H]− and [M+H]+. HPLC retention time 5.60 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 (CD3OD) δ ppm 8.50 (d, 1H, J=1.7), 8.17 (d, 1H, J=1.5), 8.12 (d, 1H, J=8.3), 7.87 (d, 1H, J=1.7), 7.80 (d, 1H, J=0.7), 7.74 (dd, 1H, J=8.0, 1.8), 7.61 (d, 1H, J=8.1), 7.52 (dd, 1H, J=8.2, 1.6), 3.75-3.68 (m, 10H), 2.61-2.54 (m, 8H), 1.49 (s, 6H).

Provenance & Evidence