反应详情

DIC (302 mg, 2.4 mmol) was added with stirring to a DMF (4 mL) solution of dasatinib (196 mg, 0.4 mmol), Boc-Val-OH (104 mg, 0.48 mmol), and DPTS (124 mg, 0.4 mmol). The resulting mixture was stirred at room temperature for five hours. After this period, DCM (100 mL) was added to the reaction mixture which was allowed to stir for an additional 20 minutes. The mixture was transferred into a separatory funnel and washed with 5% NaCl (100 mL×3). The organic phase was dried over Na2SO4 and the solvent removed under reduced pressure. The resulting residue was purified by column chromatography (biotage: DCM/CH3OH, CH3OH, 5-10%, 20 CV). The obtained solid was redissolved in 5.0 mL of TFA/DCM (2:3) and the solution was stirred at room temperature for one hour. TFA and DCM were removed under reduced pressure. The residue was dissolved in 150 mL of DCM and the resulting solution was washed with 5% Na2CO3 and then 5% NaCl. The desired product was obtained (160 mg, yield: 68%) as a white solid; 1H NMR (500 MHz, CD3OD). δ 0.96 (d, 3H), 0.99 (d, 3H), 2.03 (m, 1H), 2.32 (s, 3H), 2.47 (s, 3H), 2.59 (t, 4H), 2.71 (t, 2H), 3.64 (t, 4H), 4.32 (m, 2H), 6.00 (s, 1H), 7.22 (m, 2H), 7.34 (d, 1H), 8.14 (s, 1H); LC-MS (m/z) calcd., 586.2, found 587.2 [M+H]+.

1. waitAfter this period
2. stirringto stir for an additional 20 minutes
3. customThe mixture was transferred into a separatory funnel
4. washwashed with 5% NaCl (100 mL×3)
5. dry with materialThe organic phase was dried over Na2SO4
6. customthe solvent removed under reduced pressure
7. customThe resulting residue was purified by column chromatography (biotage: DCM/CH3OH, CH3OH, 5-10%, 20 CV)
8. dissolutionThe obtained solid was redissolved in 5.0 mL of TFA/DCM (2:3)
9. stirringthe solution was stirred at room temperature for one hour
10. customTFA and DCM were removed under reduced pressure
11. dissolutionThe residue was dissolved in 150 mL of DCM
12. washthe resulting solution was washed with 5% Na2CO3