Trifluoroacetic acid → 3-(5-(4-((Methylamino)methyl)phenyl)-1,3,4-oxadiazol-2-yl)-5-(4-methylcyclohex-1-enyl)pyrazin-2-amine

Participants

Reaction Steps

A suspension of tert-butyl N [[4-[5-[3-[bis(tert-butoxycarbonyl)amino]-6-bromo-pyrazin-2-yl]-1,3,4-oxadiazol-2-yl]phenyl]methyl]-N-methyl-carbamate (70 mg, 0.11 mmol), 4-ditert-butylphosphanyl-N,N-dimethyl-aniline; dichloropalladium (0.75 mg, 0.001 mmol) and K2CO3 (29 mg, 0.2 mmol) in toluene (630 μL) and water (70 μL) was heated to 80° C. for 18 h. The reaction mixture was cooled to room temperature and diluted with DCM (30 ml) and water (30 ml). The layers were separated and the organic layer was washed with 1M NaOH solution, dried over (Na2SO4), filtered and concentrated to dryness. The crude material obtained was stirred in 1:1 DCM:TFA mixture (3 mL) for 1 h. The solvents were evaporated under reduced pressure and the crude material was purified by reverse phase chromatography using 1 to 99% MeOH in water (0.05% HCl) to obtain 3-(5-(4-((methylamino)methyl)phenyl)-1,3,4-oxadiazol-2-yl)-5-(4-methylcyclohex-1-enyl)pyrazin-2-amine. 1H NMR (400 MHz, MeOD) δ 8.33-8.21 (m, 3H), 7.79-7.68 (m, 2H), 6.65 (s, 1H), 4.32 (d, J=5.3 Hz, 2H), 3.78-3.61 (m, 2H), 3.34 (d, J=5.4 Hz, 1H), 2.78 (d, J=5.3 Hz, 3H), 2.71 (d, J=14.9 Hz, 1H), 2.42 (ddd, J=22.1, 18.2, 5.7 Hz, 2H), 2.00-1.83 (m, 2H), 1.82-1.69 (m, 1H), 1.40 (dt, J=16.6, 4.6 Hz, 1H), 1.05 (t, J=5.9 Hz, 3H). LC/MS m/z 377.0[M+H]+.

Provenance & Evidence