Ethanamine, 2,2,2-trifluoro- → HCID 68466927, compound

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Reaction Steps

To a solution of 3-(tert-butoxycarbonyl)-3-azabicyclo[3.3.0]octane-7-carboxylic acid (0.100 g, 0.392 mmol) in dichloromethane (5 mL) were added oxalyl chloride (0.250 g, 1.96 mmol) and a drop of DMF, and the mixture was stirred at ambient temperature for 2 h. The solvent was evaporated and the residue (acid chloride) was vacuum dried. To the acid chloride in acetonitrile (5 mL) were added DIPEA (0.200 mL, 1.15 mmol) and 2,2,2-trifluoroethylamine (0.080 g, 0.081 mmol), and the mixture was stirred overnight at ambient temperature. The solvent was evaporated, and the crude amide was purified by silica gel column chromatography, eluting with an ethyl acetate in hexane gradient, to obtain 0.075 g of N-(2,2,2-trifluoroethyl)-3-(tert-butoxycarbonyl)-3-azabicyclo[3.3.0]octane-7-carboxamide (mixture of cis and trans isomers) as an oil. The majority of this sample (0.065 g, 0.19 mmol) was dissolved in dichloromethane (3 mL), combined with TFA (2 mL), and stirred at ambient temperature for 1 h. The solvent was evaporated, and the residue was purified by HPLC, using acetonitrile and 0.05% aqueous TFA as the mobile phase, to obtain 0.050 g of N-(2,2,2-trifluoroethyl)-3-azabicyclo[3.3.0]octane-7-carboxamide trifluoroacetate (as a mixture of cis and trans isomers), as an oil (1H NMR (CD3OD, 300 MHz): δ 3.93 (q, J=9.28 Hz, 2H), 3.38-3.21 (m, 4H), 3.02-2.80 (m, 3H), 2.32-2.22 (m, 2H), 1.74-1.62 (m, 2H); MS (m/z): 238 (M+1)). This material exhibited a Ki value at human α4β2 of 261 nM and did not pass HIS for α7.

Provenance & Evidence