反应详情

A mixture of N-(3-chloromethyl-[1,2,4]thiadiazol-5-yl)-L-leucyl-L-proline methyl ester (0.45 g, 1.2 mmol), 1-(2-pyridyl)piperazine (0.62 mL, 4 mmol), triethylamine (1.2 mL, 8 mmol) and tetra-butylammonium bromide (100 mg) in DMF (20 mL) was stirred at room temperature for 24 h. The reaction mixture was diluted with water and ethyl acetate. The organic layer was collected, washed with water, dried (sodium sulfate), filtered and concentrated in vacuo to give a light yellow oil. Purification by column chromatography on silica gel using a solvent mixture of 5% methanol in dichloromethane afforded N-{3-[1-[4-(2-pyridyl)piperazinyl]-methyl]-[1,2,4]thiadiazol-5-yl}-L-leucyl-L-proline methyl ester as a white foam (0.55 g, 91.7 %). 1H-NMR (CDCl3) δ8.19 (m, 1H), 7.48-7.52 (m, 1H), 7.14 (br. m, 1H, NH), 6.64-6.67 (m, 2H), 4.67 (m, 1H, CHCO), 4.57 (dd, J=8.4 and 4.6 Hz, 1H, CHCO2), 3.92 (m, 1H, NCHpro), 3.62-3.78 (m, 1OH, OMe, NCHpro, N=CCH2, 2NCH2), 2.83 (m, 4H, 2NCH2), 1.62-2.30 (m, 6H, 2CH2 pro and CH2), 0.90-1.03 (2d, J=6.5 and 6.6 Hz, 7H, 2Me and 1CH); MS (m/z) 502 (M+ +1), 459, 408, 382, 300, 253, 225, 176, 147, 121, 95.

1. customThe organic layer was collected
2. washwashed with water
3. dry with materialdried (sodium sulfate)
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customto give a light yellow oil
7. customPurification by column chromatography on silica gel using
8. additiona solvent mixture of 5% methanol in dichloromethane