反应详情

2-Trifluoromethylquinoline-6-carboxylic acid (100 mg, 0.415 mmol) was dissolved in DCM (10 mL) and N,N-di-iso-propylethylamine (Hunig's base, 268 μl, 1.54 mmol) was added. HATU (158 mg, 0.415 mmol) was added followed by (1R)-1-[1,5-dimethyl-1H-pyrazol-4-yl]ethanamine dihydrochloride (88 mg, 0.415 mmol) and the solution was stirred at RT overnight. The reaction mixture was concentrated and the residue was dissolved in EtOAc (65 mL) then partitioned with sat. aq. NaHCO3 (2×20 mL) and then brine (30 mL). The organic layer dried over MgSO4, filtered and solvent removed under reduced pressure to give a golden oil/gum. The product was purified using an ISCO (12 g column), eluting with EtOAc:Heptane (5:95 increasing to 100:0). Fractions containing pure product concentrated under reduced pressure to give a white foamy solid, 150 mg, yield=41%. 1H NMR (400 MHz, CD3OD) δ 8.68 (1H, d), 8.47-8.49 (1H, m), 8.20-8.23 (2H, m), 7.92 (1H, d), 7.48 (1H, s), 5.29 (1H, q) 3.76 (3H, s), 2.33 (3H, s) and 1.61 (3H, d). LCMS (2 min run): UV (1.37 min, 82%); ELSD (1.37 min, 100%). Mass ion: 363=MH+

1. concentrationThe reaction mixture was concentrated
2. dissolutionthe residue was dissolved in EtOAc (65 mL)
3. customthen partitioned with sat. aq. NaHCO3 (2×20 mL)
4. dry with materialThe organic layer dried over MgSO4
5. filtrationfiltered
6. customsolvent removed under reduced pressure
7. customto give a golden oil/gum
8. customThe product was purified
9. washeluting with EtOAc:Heptane (5:95 increasing to 100:0)
10. additionFractions containing pure product
11. concentrationconcentrated under reduced pressure
12. customto give a white foamy solid, 150 mg, yield=41%
13. customLCMS (2 min run)
14. customUV (1.37 min, 82%)
15. customELSD (1.37 min, 100%)