反应详情

温度

0 °C

Potassium tert-butoxide (1.0 M in THF, 0.55 ml, 0.55 mmol, 2.7 equiv) is added dropwise at room temperature under an atmosphere of argon to a solution of (1H-indol-3-yl)-oxo-acetic acid methyl ester (45 mg, 0.22 mmol, 1.1 equiv) and of 2-(6-dimethylaminomethyl-imidazo[1,2-a]pyridin-3-yl)-acetamide (50 mg, 0.20 mmol) in anhydrous tetrahydrofuran (5.0 ml, dried over molecular sieves). The reaction mixture is stirred for 30 minutes at 0° C. It is then diluted with EtOAc and poured into a saturated aqueous NH4Cl solution. After three extractions with EtOAc, the combined organic layers are dried over Na2SO4, filtered and concentrated in vacuo. The residue is dissolved in N,N-dimethylformamide (5 ml), treated with DBU (0.27 ml, 1.8 mmol, 8.9 equiv) and heated to 110° C. for 10 minutes. After cooling, the reaction mixture is diluted with water and extracted three times with CH2Cl2. The combined organic layers are ished with brine, dried over Na2SO4, filtered and concentrated in vacuo. Purification of the residue via preparative HPLC affords the title compound (34 mg, 43%) as its trifluoroacetate salt. 1H NMR (400 MHz, d6-DMSO): δ=12.11 (s, 1H), 11.27 (s, 1H), 9.47 (br s, 1H), 8.21 (d, J=2.9 Hz, 1H), 8.05 (s, 1H), 7.78-7.76 (m, 2H), 7.73 (d, J=8.0 Hz, 1H), 7.29 (dd, J=8.0/4.0 Hz, 1H), 6.94 (t, J=8.0 Hz, 1H), 6.49 (t, J=8.0 Hz, 1H), 5.95 (d, J=8.0 Hz, 1H), 3.48-3.40 (m, 2H), 2.16 (s, 6H). MS (ES+): 386 (M+H)+.

1. extractionAfter three extractions with EtOAc
2. dry with materialthe combined organic layers are dried over Na2SO4
3. filtrationfiltered
4. concentrationconcentrated in vacuo
5. dissolutionThe residue is dissolved in N,N-dimethylformamide (5 ml)
6. temperatureheated to 110° C. for 10 minutes
7. temperatureAfter cooling
8. extractionextracted three times with CH2Cl2
9. dry with materialdried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customPurification of the residue via preparative HPLC