4-Methylmorpholine → HCID 67995196, compound

Participants

Reaction Steps

A mixture of 2-((3-(7-acetyl-4-carbamoyl-5H-pyridazino[4,5-b]indol-1-yl)-2-methylphenylamino)methyl)-5-methoxybenzoic acid (0.336 g, the crude product from previous step), BOP (0.852 g, 1.925 mmol), and N-methylmorpholine (0.635 mL, 5.78 mmol) in DMF (4 mL) was stirred at 45° C. for 1 hr. The mixture was diluted with ethyl acetate (100 mL), washed with water (2×25 mL) and brine (25 mL), and dried over anhydrous MgSO4. After solvent was removed under vacuum, the residue were divided into 4 portions and purified by reverse phase HPLC. The correct fractions were combined and concentrated under vacuum, basified with saturated NaHCO3 solution, and extracted with ethyl acetate (3×35 mL). The combined extract was washed with brine (30 mL) and dried over anhydrous MgSO4. Removal of solvent under vacuum provided the desired product (40 mg, 0.077 mmol, 11% yield over 3 steps) as a yellow solid. LCMS (M+H)+=506.29. 1H NMR (500 MHz, DMSO-d6) δ: 12.67 (s, 1H), 8.83 (s, 1H), 8.52 (s, 1H), 8.09 (s, 1H), 7.83 (dd, J1=8.5 Hz, J2=1.5 Hz, 1H), 7.77 (dd, J1=7.8 Hz, J2=1.1 Hz, 1H), 7.63-7.60 (m, 2H), 7.55 (d, J=6.4 Hz, 1H), 7.47 (d, J=8.3 Hz, 1H), 7.33 (d, J=2.5 Hz, 1H), 7.27 (dd, J1=8.3 Hz, J2=2.5 Hz, 1H), 5.02 (d, J=17.2 Hz, 1H), 4.91 (d, J=17.2 Hz, 1H), 3.86 (s, 3H), 2.68 (s, 3H), 1.89 (s, 3H).

Provenance & Evidence