Methanol → 3-methoxy-N-[(3R)-1-methylpyrrolidin-3-yl]-4-[(4,4,6-trimethyl-5-oxo-2-propan-2-yl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl)amino]benzamide

Participants

Reaction Steps

10-chloro-4,4,6-trimethyl-2-propan-2-yl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one (Intermediate 178; 75 mg, 0.27 mmol), 4-amino-3-methoxy-N-(1-methylpyrrolidin-3-yl)benzamide (Intermediate 187; 67 mg, 0.27 mmol) and p-toluenesulphonic acid monohydrate (127 mg, 0.66 mmol) were heated at 140° C. in 4-methyl-2-pentanol (4 mL) for 2 hours. The reaction mixture was loaded onto an SCX-3 column pre-wet with methanol. The column was washed with methanol and eluted with 2% 7N ammonia/methanol to. Product containing fractions were evaporated and the residue dissolved in DMF and purified by base modified reverse phase HPLC to give the title compound as a white solid (23 mg, 17.5%).

Provenance & Evidence