反应详情

Into a 25-mL round-bottom flask, was placed 160 mg of tert-butyl 4-(2-(methyl(3-((4-(piperidin-1-yl)-2-(4-((3-(trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)phenyl)-carbamoyl)benzyl)amino)ethyl)piperazine-1-carboxylate Example 38 and 10 mL of 1:1 dichloromethane/TFA. After stirring for 2 hours, the solvent was evaporated. The residue was partitioned between ethyl acetate and aqueous sodium bicarbonate solution. The organic phase was dried and the solvent was evaporated. The residue was treated with triethylamine (78 mg, 0.77 mmol, 6.00 equiv), and dichloromethane (2 mL). This was followed by dropwise addition of a solution of methanesulfonyl chloride (21.9 mg, 0.19 mmol, 1.50 equiv) in dichloromethane (1 mL) with stirring at 0° C. The resulting solution was stirred for 4 h at 25° C. The resulting mixture was concentrated under vacuum. The crude product (200 mg) was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained as 45 mg (28%) of a yellow solid. 1H-NMR (300 MHz, DMSO-d6, ppm): δ 12.31 (s, 1H), 9.55-9.59 (t, J=6.6 Hz, 1H), 8.93-8.94 (d, J=3 Hz, 1H), 8.35 (s, 1H), 8.27-8.30 (d, J=9 Hz, 1H), 8.09 (s, 1H), 7.96-7.98 (d, J=6 Hz, 1H), 7.85-7.86 (d, J=3 Hz, 1H), 7.56-7.76 (m, 7H), 7.31-7.34 (d, J=9 Hz, 1H), 4.62-4.64 (d, J=6 Hz, 2H), 4.39 (s, 2H), 3.34 (s, 4H), 3.22-3.24 (d, J=6 Hz, 6H), 2.90 (s, 5H), 2.74 (s, 3H), 2.69 (s, 4H), 1.75 (s, 4H), 1.60-1.61 (d, J=3 Hz, 2H). MS (ES, m/z): 792 [M+H]+.

1. customInto a 25-mL round-bottom flask, was placed
2. customthe solvent was evaporated
3. customThe residue was partitioned between ethyl acetate and aqueous sodium bicarbonate solution
4. customThe organic phase was dried
5. customthe solvent was evaporated
6. stirringwith stirring at 0° C
7. stirringThe resulting solution was stirred for 4 h at 25° C
8. concentrationThe resulting mixture was concentrated under vacuum
9. customThe crude product (200 mg) was purified by reverse phase HPLC
10. washeluting with a water/CH3CN gradient
11. additioncontaining 0.05% TFA