反应详情

A mixture of 2-[4-(7-methyl-4-morpholin-4-yl-2-(tributylstannanyl)thieno[3,2-d]pyrimidin-6-ylmethyl)piperazin-1-yl]isobutyramide (200 mg, 0.28 mmol), 4-bromo-pyrrolo[2,3-b]pyridine-1-carboxylic acid tert-butylester (100 mg, 0.34 mmol), Pd(Ph3)4 (33 mg, 0.028 mmol) and CuI (65 mg, 0.34 mmol) in toluene (5 mL) was purged with argon, then subjected to microwave irradiation at 140° C. for 30 min. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the desired product was eluted using 2 M NH3 in MeOH. The residue was then dissolved in DCM/TFA (8 mL/8 mL) and stirred for 2 h at room temperature. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the desired product was eluted using 2 M NH3 in MeOH. The residue was purified by column chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 05:95) to give 696 as a white powder (0.036 g, 24%). LCMS (Method F): RT 5.68 min, [M+H]+ 535.2. 1H NMR (CDCl3, 400 MHz) δ 9.42-8.74 (m, 1 H); 8.59-7.95 (m, 1 H); 7.92-7.49 (m, 1 H); 7.46-7.35 (m, 2 H); 7.14-7.06 (m, 1 H); 5.27 (s, 1 H); 4.09 (t, J=4.2 Hz, 4); 3.92 (t, J=4.2 Hz, 4 H); 3.85 (s, 2 H); 2.66-2.61 (m, 4 H); 2.53 (s, 3 H); 1.63-1.58 (m, 4 H); 1.26 (s, 6 H)

1. customwas purged with argon
2. customirradiation at 140° C. for 30 min
3. washThe cartridge was washed with MeOH
4. washthe desired product was eluted
5. dissolutionThe residue was then dissolved in DCM/TFA (8 mL/8 mL)
6. washThe cartridge was washed with MeOH
7. washthe desired product was eluted
8. customThe residue was purified by column chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 05:95)