反应详情

温度

150 °C

A mixture of 4-morpholin-4-yl-6-(3-morpholin-4-yl-azetidin-1-ylmethyl)-2-(tributylstannanyl)thieno[3,2-d]pyrimidine (192 mg, 0.29 mmol), 1-benzenesulfonyl-4-bromo-1H-pyrrolo[3,2-c]pyridine (117 mg, 0.35 mmol), tetrakis(triphenylphosphine)palladium (34 mg, 10 mol %) and copper(I)-thiophene-2-carboxylate (11 mg, 20 mol %) in dioxane (2.0 mL) was purged with argon gas then heated at 150° C., for 20 min, in a microwave reactor. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge, washed with MeOH/DCM then eluted with 2 M NH3 in MeOH. The resulting residue was dissolved in IMS/dioxane (1:1 mL) and 12.5 M aqueous NaOH solution (0.1 mL) added. After stirring for 1 h the reaction mixture was loaded onto an Isolute® SCX-2 cartridge, washed with MeOH/DCM then eluted with 2 M NH3 in MeOH/DCM. The resulting residue was purified by column chromatography (Si—PCC, 2 M NH3 in MeOH:DCM, gradient 0:100 to 10:90) followed by trituration from diethyl ether to give 174 (38 mg, 27%) as a pale yellow solid. LCMS RT 4.52 min, [M+H]+ 492. 1H NMR (CDCl3, 400 MHz) δ 8.53 (m, 1 H), 7.45-7.35 (m, 4 H), 4.10 (t, J=4.7 Hz, 4 H), 3.97 (s, 2 H), 3.89 (t, J=4.7 Hz, 4 H), 3.72 (t, J=4.5 Hz, 4 H), 3.69-3.54 (m, 2 H), 3.08-3.01 (m, 3H), 2.33 (m, 4 H).

1. customwas purged with argon gas
2. washwashed with MeOH/DCM
3. washthen eluted with 2 M NH3 in MeOH
4. dissolutionThe resulting residue was dissolved in IMS/dioxane (1:1 mL)
5. addition12.5 M aqueous NaOH solution (0.1 mL) added
6. washwashed with MeOH/DCM
7. washthen eluted with 2 M NH3 in MeOH/DCM
8. customThe resulting residue was purified by column chromatography (Si—PCC, 2 M NH3 in MeOH:DCM, gradient 0:100 to 10:90)