反应详情

4-[7-(3-piperazin-1-yl-propoxy)-quinazolin-4-yl]-piperidine-1-carboxylic acid tert-butyl ester (0.05 mmol), prepared as described in Example 118, was dissolved in anhydrous DCM (1 mL) and treated with Et3N (0.05 mmol) followed by FMOC-Cl (0.1 mmol) and the mixture was stirred at rt overnight and then washed with water thrice, then dried over anhydrous MgSO4, filtered and concentrated in vacuo. To this was added 3M HCl/MeOH (1 mL) and the mixture was stirred at rt for 2 h and then concentrated in vacuo and the residue was dissolved in a 1:1 mixture of DCM:MeOH, neutralized with excess Et3N and treated with (4-morpholin-4-yl-phenyl)-carbamic acid 4-nitrophenyl ester hydrochloride (0.06 mmol), as prepared by the method outlined in Example 66a. The mixture was stirred at rt overnight and then concentrated in vacuo and partitioned between water and DCM. DCM layer was drawn off, washed with water thrice, then dried over anhydrous MgSO4, filtered and concentrated in vacuo. The residue was purified by Preparative TLC (silica gel; DCM:MeOH:NH4OH; 90:9:1) to obtain the pure product. This was dissolved in anhydrous DCM (1 mL) and diethylamine (0.25 mL) was added and the mixture was stirred at rt overnight. It was then concentrated in vacuo and purified by Preparative TLC (silica gel; DCM:MeOH:NH4OH; 90:9:1) to obtain 2.8 mg (10%) of the title compound. 1H-NMR (300 MHz, CDCl3): 9.13 (s, 1H), 8.05 (d, 1H), 7.35-7.23 (m, 4H), 6.88 (d, 2H), 6.35 (s, 1H), 4.32-4.14 (m, 4H), 3.90-3.80 (m, 4H), 3.75-3.60 (m, 1H), 3.20-2.91 (m, 10H), 2.75-2.55 (m, 6H), 2.18-1.85 (m, 7H). LC/MS (ESI): 560.0 (MH)+.

1. washwashed with water thrice
2. dry with materialdried over anhydrous MgSO4
3. filtrationfiltered
4. concentrationconcentrated in vacuo
5. additionTo this was added 3M HCl/MeOH (1 mL)
6. stirringthe mixture was stirred at rt for 2 h
7. concentrationconcentrated in vacuo
8. dissolutionthe residue was dissolved in a 1:1 mixture of DCM
9. customas prepared by the method
10. stirringThe mixture was stirred at rt overnight
11. concentrationconcentrated in vacuo
12. custompartitioned between water and DCM
13. washwashed with water thrice
14. dry with materialdried over anhydrous MgSO4
15. filtrationfiltered
16. concentrationconcentrated in vacuo
17. customThe residue was purified by Preparative TLC (silica gel; DCM:MeOH:NH4OH; 90:9:1)
18. customto obtain the pure product
19. stirringthe mixture was stirred at rt overnight
20. concentrationIt was then concentrated in vacuo
21. custompurified by Preparative TLC (silica gel; DCM:MeOH:NH4OH; 90:9:1)