Cesium carbonate → 3-chloro-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-(2-dimethylaminoethyl)benzamide

Participants

Reaction Conditions

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) and 4-amino-3-chloro-N-(2-dimethylaminoethyl)benzamide (Intermediate 213; 89 mg, 0.37 mmol) were dissolved in 1,4 dioxane (4 mL) and caesium carbonate (234 mg, 0.72 mmol) was added. The reaction mixture was sparged with nitrogen for 15 minutes prior to addition of tris-dibenzylideneacetone dipalladium (II) (19 mg, 0.02 mmol) followed by XANTPHOS (19 mg, 0.03 mmol). The reaction mixture was heated at 100° C. overnight, cooled to room temperature and diluted with DCM (20 mL). The resultant mixture was filtered and the filtrate loaded onto an SCX-3 (5 g) cartridge. The cartridge was washed through with methanol (50 mL) and then eluted with 2M ammonia in methanol (50 mL). Evaporation of the ammoniacal fraction afforded an amber gum which was purified by acid modified reverse phase preparative HPLC. The resultant material was dissolved in MeOH/Water and poured onto an SCX-3 cartridge (2 g) and cartridge which was then washed with methanol and eluted with 2M ammonia in methanol, and the ammoniacal solution evaporated to yield the title compound as a solid (7 mg, 3%).

Provenance & Evidence