反应 #1810

反应方程式

EDC

HCl.H2N-Gly-Asp(OBn)-Phe-OBn

diisopropylethylamine

dimethylformamide

HOBT

→

3-[6-Amino-2-pyridinyl]-propionyl-glycyl-(L)-aspartyl-(L)-phenylalanine

收率 10.0%

溶剂

ethanol

反应条件

后处理

1. 1
   温度to warm to room temperature
2. 2
   其他the dimethylformamide was removed on a rotovap at 40° C
3. 3
   其他The residue was partitioned between ethyl acetate and water
4. 4
   洗涤the organic layer rinsed one time with water, two times with 5% citric acid
5. 5
   其他The organic solution was dried on sodium sulfate
6. 6
   其他the ethyl acetate removed
7. 7
   其他From this solution was recovered 85 mg (55%) of the starting peptide
8. 8
   萃取extracted with dichloromethane
9. 9
   其他thus obtained on silica gel using 5% methanol/methylene chloride
10. 10
    其他The product thus obtained (30 mg, 0.5 mmol)
11. 11
    其他The flask was flushed with H2
12. 12
    workup.ADDITIONso an additional 7 mg of 10% Pd/C was added
13. 13
    其他After 24 additional hours, the solvents were removed
14. 14
    其他a roto-evaporator
15. 15
    workup.ADDITIONthe residue treated with 1% acetic acid in water
16. 16
    过滤The solution was filtered
17. 17
    其他purified

实验过程

3-(2-[6-Aminopyridyl])-propionic acid (63 mg, 0.28 mmol), HOBT (50 mg, 0.37 mmol), HCl.H2N-Gly-Asp(OBn)-Phe-OBn (155 mg, 0.28 mmol) and diisopropylethylamine were combined in 7 ml of dry dimethylformamide. The reaction mixture was cooled to 0° C. EDC (68 mg, 0.35 mmol) was added in one portion, the reaction mixture allowed to warm to room temperature and placed under argon. After 18 hours, the dimethylformamide was removed on a rotovap at 40° C. The residue was partitioned between ethyl acetate and water, and the organic layer rinsed one time with water, two times with 5% citric acid, once again with water, twice with 5% sodium bicarbonate solution, again with water, and finally one time with brine. The organic solution was dried on sodium sulfate, and the ethyl acetate removed. From this solution was recovered 85 mg (55%) of the starting peptide. The combined aqueous rinses were adjusted to pH 9 using dilute NaOH, and extracted with dichloromethane. Chromatography was carried out on the oil thus obtained on silica gel using 5% methanol/methylene chloride. The product thus obtained (30 mg, 0.5 mmol) was dissolved in 5 ml of ethanol, and treated with 10% Pd/C (wetted with butanol) (10 mg). The flask was flushed with H2, and stirred under an atmosphere of H2 for 18 hours. After this time, TLC showed some starting material, so an additional 7 mg of 10% Pd/C was added, and the reaction mixture placed again under H2. After 24 additional hours, the solvents were removed using a roto-evaporator, and the residue treated with 1% acetic acid in water. The solution was filtered, and purified using HPLC. This afforded 19 mg of the desired product as a white powder. Overall yield: 10%. NMR (CD3OD): 7.79 ("t", 1H, J=8.1); 7.22 (m, 5H); 6.81 (d, 1H, J=9.0); 6.73 (d, 1H, J=7.2); 4.74 ("t", 1H, J=5.1); 4.61 (m, 1H); 3.85 (s, 2H); 3.18 ("a-b"d, 1H, J=4.5); 3.02 (m, 3H); 2.79 ("a-b"d, 1H, J=5.0); 2.66 (m, 3H). Mass spectrum: 484 (m-H)- ; 598 (M+CF3COO-). EA: Calculated for C23H27N5O7.2.5 F3C3O2H.2.5 H2O: C, 41.24; H, 4.22; N, 8.59. Found: C, 41.30; H, 4.26; N, 8.81.

来源