反应详情

温度

80 °C

To a mixture of 4-[5-(5-diethylaminomethyl-4-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenol (700 mg, 1.82 mmol) and K2CO3 (760 mg, 5.45 mmol) in acetonitrile (14 mL), 2-(Boc-amino)-ethylbromide (839 mg, 3.63 mmol) is added. The mixture is stirred at 80° C. for 12 h. The mixture is filtered and the filtrate is concentrated. The residue is dissolved in DCM (10 mL) and treated with TFA (1.4 mL). The mixture is stirred at rt for 19 h before another portion of TFA (0.7 mL) is added. Stirring is continued at rt for another 21 h. The mixture is diluted with DCM and washed with 1 M aq. NaOH. The washing is extracted back with DCM. The combined organic extracts are dried over MgSO4, filtered and concentrated. The crude product is purified by prep. HPLC. The product containing fractions are combined, concentrated, dissolved in methanol:water 9:1 and filtered over Amberlyst A-21. The filtrate is evaporated and dried to give the title compound (513 mg) as a pale yellow resin; LC-MS: tR=0.44 min; [M+1]+=429.20; 1H NMR (D6-DMSO): δ1.03 (t, J=7.0 Hz, 6H), 1.23 (t, J=7.5 Hz, 3H), 2.22 (s, 3H), 2.35 (s, 3H), 2.58 (q, J=7.3 Hz, 4H), 2.73 (q, J=7.5 Hz, 2H), 3.05 (t, J=5.5 Hz, 2H), 3.73 (s, 3H), 3.86 (t, J=5.5 Hz, 2H), 7.75 (s, 2H), 7.80 (s, 1H).

1. additionis added
2. filtrationThe mixture is filtered
3. concentrationthe filtrate is concentrated
4. dissolutionThe residue is dissolved in DCM (10 mL)
5. additiontreated with TFA (1.4 mL)
6. stirringThe mixture is stirred at rt for 19 h before another portion of TFA (0.7 mL)
7. additionis added
8. stirringStirring
9. waitis continued at rt for another 21 h
10. additionThe mixture is diluted with DCM
11. washwashed with 1 M aq. NaOH
12. extractionThe washing is extracted back with DCM
13. dry with materialThe combined organic extracts are dried over MgSO4
14. filtrationfiltered
15. concentrationconcentrated
16. customThe crude product is purified by prep
17. additionThe product containing fractions
18. concentrationconcentrated
19. dissolutiondissolved in methanol:water 9:1
20. filtrationfiltered over Amberlyst A-21
21. customThe filtrate is evaporated
22. customdried