Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → tert-butyl 1-(1-(4-chlorophenyl)-2-(4-((S)-5-methyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)piperazin-1-yl)-2-oxoethyl)cyclopropylcarbamate

Participants

Reaction Steps

HBTU (0.097 mmol, 47 mg) was added to a solution of (S)-5-methyl-4-(piperazin-1-yl)-5,7-dihydrothieno[3,4-d]pyrimidine dihydrochloride (30 mg, 0.097 mmol) and 2-(1-(tert-butoxycarbonylamino)cyclopropyl)-2-(4-chlorophenyl)acetic acid (0.097 mmol) in DCM (5 mL) and TEA (5 mL). The mixture was stirred at room temperature for 6 hours. The solvent was removed, and the residue was subject to column chromatography, eluted by DCM/MeOH (50:1) to give tert-butyl 1-(1-(4-chlorophenyl)-2-(4-((S)-5-methyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)piperazin-1-yl)-2-oxoethyl)cyclopropylcarbamate LCMS: 544.0 [M-Boc+H+] (APCI+); Rf: 3.49 min. The tert-butyl 1-(1-(4-chlorophenyl)-2-(4-((S)-5-methyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)piperazin-1-yl)-2-oxoethyl)cyclopropylcarbamate was deprotected using procedures described previously to give 2-(1-aminocyclopropyl)-2-(4-chlorophenyl)-1-(4-((S)-5-methyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)piperazin-1-yl)ethanone. Rf: 2.24 min.

Provenance & Evidence