Chloroacetyl chloride → 2-Chloro-1-[2-(indan-2-ylamino)-5,7-dihydropyrrolo[3,4-d]pyrimidin-6-yl]ethanone

Participants

Reaction Conditions

Reaction Steps

Stir a suspension of N-(2,3-dihydro-1H-inden-2-yl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-amine dihydrochloride hydrate (14.4 g, 41.9 mmol) and triethylamine (14.3 g, 19.7 mL, 141.4 mmol) in dichloromethane (200 mL) at 23° C. for 10 minutes, then cool to −30° C. Add 2-chloroacetyl chloride (5.49 g, 3.86 mL, 48.6 mmol) over two minutes and warm to 23° C. over 10 minutes. Add methanol (5 mL) and remove the solvent in vacuo. Slurry the crude reaction mixture in methanol (30 mL), add 50 g silica gel and remove solvent in vacuo. Load the resulting residue onto a loading column and purify via silica gel column chromatography (gradient elution: 50% ethyl acetate in hexanes to ethyl acetate to 10% methanol in ethyl acetate) to give the title compound (11.5 g, 84%). MS (m/z): 329(M+1).

Provenance & Evidence