反应详情

To 17.1 g of Nα-(2,6-dichlorobenzoyl)-4-{2-ethoxycarbonylamino-5-(N-formyl-N-methyl-aminomethyl)-benzoylamino}-L-phenylalanine isopropyl ester prepared in the foregoing step 1, there were added 68 mL of N,N-dimethylformamide, 6.8 mL of 2-propanol and 7.55 g of potassium carbonate, and then 5.89 mL of methyl p-toluene-sulfonate was added to the resulting mixture, followed by the stirring of the mixture at room temperature overnight. After confirming the completion of the reaction by HPLC, 6.25 mL of acetic acid was added to quench the mixture and then 84 mL of water was dropwise added thereto to separate out a solid material. The separated solid was isolated through filtration under reduced pressure, washed with 82 mL of water and then dried under reduced pressure to thus give 15.80 g of the intended compound as a white crystalline solid. The physical properties of the 4-amino-Nα-(2,6-dichlorobenzoyl)-L-phenylalanine methyl ester and 12 mL of N,N-dimethylformamide, and the resulting mixture was stirred overnight. Subsequently, 48 mL of methanol was dropwise added, the resulting mixture was stirred at 10° C. overnight and then the solid separated from the mixture was isolated through filtration under reduced pressure. The solid was then washed with 8 mL of methanol and dried at 70° C. for 5 hours under reduced pressure to thus give 5.50 g of the title compound as a pale yellow solid.

1. additionwas added
2. customto quench the mixture
3. addition84 mL of water was dropwise added
4. customto separate out a solid material
5. customThe separated solid was isolated through filtration under reduced pressure
6. washwashed with 82 mL of water
7. dry with materialdried under reduced pressure to thus give 15.80 g of the intended compound as a white crystalline solid
8. stirringThe physical properties of the 4-amino-Nα-(2,6-dichlorobenzoyl)-L-phenylalanine methyl ester and 12 mL of N,N-dimethylformamide, and the resulting mixture was stirred overnight
9. additionSubsequently, 48 mL of methanol was dropwise added
10. stirringthe resulting mixture was stirred at 10° C. overnight
11. customthe solid separated from the mixture
12. customwas isolated through filtration under reduced pressure
13. washThe solid was then washed with 8 mL of methanol
14. dry with materialdried at 70° C. for 5 hours under reduced pressure to thus give 5.50 g of the title compound as a pale yellow solid