p-Toluenesulfonic acid monohydrate → HCID 68683094, compound

Participants

Reaction Conditions

Reaction Steps

2′-chloro-9′-cyclohexyl-5′-methyl-8′,9′-dihydrospiro[cyclopropane-1,7′-pyrimido[5,4-b][1,4]diazepin]-6′(5′H)-one (Intermediate 270; 97 mg, 0.3 mmol) and 4-amino-3-fluoro-N-(9-methyl-9-azabicyclo[3.3.1]non-7-yl)benzamide (Intermediate 162; 88 mg, 0.3 mmol) were combined with p-toluenesulphonic acid monohydrate (143 mg, 0.75 mmol) in 4-methyl-2-pentanol (2 mL) and heated by microwave irradiation for 30 minutes at 160° C. The cooled reaction mixture was diluted with methanol (5 mL) and loaded onto an SCX-3 (5 g) cartridge pre-wet with methanol. The cartridge was washed with methanol (2×10 mL) and product eluted with 7 N methanolic ammonia (20 mL). Product containing fractions were evaporated and the resultant material purified by base modified reverse phase preparative HPLC to yield the title compound as a white solid (82 mg, 48%).

Provenance & Evidence