Methanol → 4-(9'-cyclopentyl-5'-methyl-6'-oxo-5',6',8',9'-tetrahydrospiro[cyclopropane-1,7'-pyrimido[5,4-b][1,4]diazepine]-2'-ylamino)-N-(1-ethyl-4-piperidyl)-3-methoxy-benzamide

Participants

Reaction Steps

2′-chloro-9′-cyclopentyl-5′-methyl-8′,9′-dihydrospiro[cyclopropane-1,7′-pyrimido[5,4-b][1,4]diazepin]-6′(5′H)-one (Intermediate 130; 100 mg, 0.33 mmol), 4-amino-N-(1-ethyl-4-piperidyl)-3-methoxy-benzamide (Intermediate 190; 91 mg, 0.33 mmol) and p-toluenesulphonic acid monohydrate (156 mg, 0.81 mmol) were heated at 140° C. in 4-methyl-2-pentanol (4 mL) for 2 hours. The reaction mixture was loaded onto to an SCX-3 cartridge (10 g) pre-wet with methanol, then washed with methanol and eluted with 2% 7N ammonia/methanol. Product containing fractions were combined and evaporated and the resultant material purified by base modified reverse phase preparative HPLC to yield the title compound as a white solid (89 mg, 50%).

Provenance & Evidence