HCID 58154169, compound → 2'-chloro-9'-cyclopentyl-8',9'-dihydrospiro[cyclopropane-1,7'-pyrimido[4,5-b][1,4]diazepin]-6'(5'H)-one

Participants

Reaction Conditions

Reaction Steps

Ethyl1-[[(2-chloro-5-nitro-pyrimidin-4-yl)-cyclopentyl-amino]methyl]cyclopropane-1-carboxylate (Intermediate 132; 35.92 g, 97.4 mmol) was dissolved in the acetic acid (750 mL) and the solution stirred and heated to 70° C. under nitrogen. Iron powder (14.61 g) was added in portions over 10 minutes. Over the next 10-15 minutes the resulting exotherm took the reaction mixture temperature up to a maximum of 92° C. The temperature then slowly dropped back to 75° C. The dark reaction mixture was then stirred at 75° C. for 3 hours. The reaction mixture was filtered whilst still hot through a bed of celite and the bed washed through with DCM. The acetic acid/DCM filtrate was evaporated to dryness and the resulting residue azeotroped three times with toluene. The residue was left under high vacuum at room temperature overnight, taken up in DCM and filtered through a small bed of celite. The celite was washed with DCM and the filtrate concentrated down to 250 mL and loaded onto a dry silica column pre-conditioned with DCM. The column was eluted with a 5-10% gradient of 7N NH3/MeOH in DCM and product containing fractions were combined and evaporated. The resultant material was recrystallised from isopropanol. The solid precipitate was collected by filtration, washed with chilled isopropanol and dried by desiccation under high vacuum at room temperature to constant weight to yield the title compound as a grey solid (17.1 g.

Provenance & Evidence