Trifluoromethanesulfonic acid → 2-(4-(3-Methyl-5-phenylpyrazin-2-yl)piperazin-1-yl)pyrimidine

Participants

Reaction Conditions

Reaction Steps

This compound was prepared via the pyrazine triflate with 1-(2-pyrimidyl)piperazine as the amine following the procedure of Adams et al (Synlett 2004, 11, 2031-2033). Pyridine was used as an anhydrous reagent kept under argon in a sure-seal bottle (Aldrich). The compound 24 (100 mg, 0.52 nmol) and DMAP (65.7, 0.52 mmol) were dissolved in pyridine and methylene chloride (0.5:4 ml v/v), and cooled to 0° C. The trifluoromethane sulfonic acid (0.8 mmol, 135.5 μL) was added dropwise and stirred for 15 min at 0° C. and then 3 h at RT. The triflate was confirmed by ESI (363.7 (MH+)) and HPLC (tR=25.33 min). The reaction mixture was diluted with dichloromethane and washed one time each with 20 ml of water, sodium bicarbonate and brine. The dichloromethane was removed under reduced pressure, and the remaining residue was dissolved directly in DMSO. 1-(2-pyrimidyl)piperazine (5.3 mmol, 750 μL) was added and the reaction heated to 60° C. and stirred for 2 h. When complete, the reaction was diluted with ethyl acetate and washed with 1N HCl, after washes with brine and water to remove remaining pyridine. The organics were then dried and evaporated in vacuo to give 25 as a yellow solid (63% yield). HPLC (tr/purity): 24.74 min, >98%. ESI m/z (CH2Cl2) 333.29 (MH+). 1H NMR (500 MHz, CDCl3): δ 8.56 (s, 1H); 8.36 (d, J=4 Hz, 2H); 8.01 (d, J=7.5 Hz, 2H); 7.48-7.40 (m, 3H); 6.54 (bs, 1H); 4.03 (bs, 4H), 3.42 (bs, 4H); 2.62 (s, 6H). HRMS calculated GIVEN Apr. 21, 2006

Provenance & Evidence