Trifluoroacetic acid → HCID 90424043, compound

Participants

Reaction Steps

Add trifluoroacetic acid (3 mL) to a flask containing tert-butyl 2-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-6-yloxylacetate (0.30 g; 2.04 equiv; 1.19 mmoles) in dichloromethane (3 mL), and stir at ambient temperature for 1 hour. Concentrate the mixture, add toluene (2×5 mL), and reconcentrate (2×). Add methanol (10 mL) followed by 5 N hydrochloric acid (1 mL), then concentrate. Add toluene (4×5 mL) and reconcentrate (4×). Add dimethylformamide (5 mL), triethylamine (15 equiv; 8.74 mmol; 1.22 mL), N-(2,3-dihydro-1H-inden-2-yl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-amine dihydrochloride hydrate (0.20 g; 1.0 equiv; 0.583 mmoles) and 1-propanephosphonic acid cyclic anhydride (0.70 mL; 2.0 equiv; 1.17 mmoles) and stir at ambient temperature for 2 hours. Load the solution directly onto a silica gel column and purify by column chromatography (hexanes to ethyl acetate to 20% methanol in ethyl acetate) to give impure product. Further purify the crude product by reverse phase chromatography to afford 1-[2-(2,3-dihydro-1H-inden-2-ylamino)-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidin-6-yl]-2-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-6-yloxy)ethanone (0.083 g; 33%) as a light yellow foam. MS (m/z): 431(M+1).

Provenance & Evidence