Ethylenediamine → Trifluoroacetic acid

Participants

Reaction Conditions

Reaction Steps

To a mixture of (±)-3-chloro-1′-{[2-(trimethylsilyl)ethoxy]methyl}-5,7-dihydrospiro[cyclopenta[c]pyridine-6,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (0.404 g, 1.004 mmol, described in Intermediate 32) and tert-butyl (5R)-4-allyl-5-(3,5-difluorophenyl)-2,2,5-trimethyl-3-oxopiperazine-1-carboxylate (0.36 g, 0.913 mmol) in degassed DMA (5.4 mL) in a large microwave vessel was added N,N-dicyclohexylmethylamine (0.215 mL, 1.00 mmol) and the mixture was degassed for 5 min. To the resulting mixture was added bis(tri-t-butylphosphine)palladium(0) (0.154 g, 0.301 mmol) and the mixture was degassed again. The reaction mixture was heated in a microwave reactor for 20 minutes at 150° C., cooled to ambient temperature, and filtered. The filtrate was partitioned between EtOAc (100 mL) and H2O (50 mL). The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. To the crude alkene in CH2Cl2 (10 mL) was added TFA (1.05 mL, 13.6 mmol) and the resulting mixture was stirred at room temperature for 30 min. The mixture was concentrated under reduced pressure, dissolved in MeOH and 1 N sodium hydroxide (2.73 mL, 2.73 mmol) and ethylenediamine (0.323 mL, 4.79 mmol) were added. The reaction mixture was stirred for 12 h at ambient temperature, concentrated in vacuo, and purified by HPLC using a reversed phase C18 column and eluting with a gradient of H2O:CH3CN:CF3CO2H—90:10:0.1 to 5:95:0.1, to give the title compound. MS: m/z=530 (M+1), HRMS: m/z=530.2360 (M+1); calculated m/z=530.2362 (M+1) for C30H30F2N5O2.

Provenance & Evidence