4-Methylmorpholine → HCID 67995603, compound

Participants

Reaction Steps

A yellow, homogeneous solution of 1-(3-(6-chloro-1-oxoisoindolin-2-yl)-2-methylphenyl)-7-(2-methoxyethoxy)-5H-pyridazino[4,5-b]indole-4-carboxylic acid (0.0206 g, 0.038 mmol), ammonium chloride (8.12 mg, 0.152 mmol), DIPEA (0.032 mL, 0.182 mmol), N-methylmorpholine (5.42 μL, 0.049 mmol) and BOP (0.065 g, 0.148 mmol) in DMF (0.379 mL) was stirred for 1 hr. It was diluted with MeOH (1 mL) and purified by reverse phase HPLC. The appropriate fractions were collected, basified with NaHCO3 (solid), and concentrated in vacuo. The residue was extracted with CH2Cl2 (3×). The combined extract was dried over Na2SO4 and concentrated in vacuo to give the desired product (0.0064 g, 0.012 mmol, 30.9% yield) as a white solid. LC/MS (M+H)=542.15; 1H NMR (500 MHz, DMSO-d6) (recognizable peaks for major atropoisomer) δ ppm 12.22 (s, 1H), 8.71 (s, 1H), 7.98 (s, 1H), 7.80-7.85 (m, 1H), 7.74-7.76 (m, 2H), 7.73 (d, J=1.1 Hz, 1H), 7.58 (s, 1H), 7.53 (d, J=1.1 Hz, 1H), 7.41 (d, J=2.2 Hz, 1H), 7.19 (d, J=8.9 Hz, 1H), 6.87 (d, J=2.2 Hz, 1H), 5.05 (d, J=17.8 Hz, 1H), 4.98 (d, J=17.5 Hz, 1H), 4.14-4.21 (m, 2H), 3.72 (dd, J1=5.4 Hz, J2=3.8 Hz, 2H), 3.32 (s, 3 H), 1.88 (s, 3 H).

Provenance & Evidence