4-Bromo-1H-pyrrolo(2,3-c)pyridine → 2-Methyl-2-(4-((4-morpholino-2-(1h-pyrrolo[2,3-c]pyridin-4-yl)thieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)propanamide

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-[4-(4-morpholin-4-yl-2-(tributlystannanyl)thieno[3,2-d]pyrimidin-6-ylmethyl)piperazin-1-yl]isobutyramide (1.17 g, 1.69 mmol), 4-bromo-1H-pyrrolo[2,3-c]pyridine (432 mg, 2.19 mmol), tetrakis(triphenylphosphine)palladium (194 mg, 10 mol %) and CuI (385 mg, 2.02 mmol) in dioxane (20 mL) was purged with argon gas then heated at 140° 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/DCM. The resulting residue was purified by column chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 20:80). The resulting solid was dissolved in MeOH, loaded onto an Isolute® SCX-2 cartridge, washed with MeOH then eluted with 2 M NH3 in MeOH to afford 105 as a pale yellow solid (242 mg, 39%). LCMS (Method F): RT 4.51 min, [M+H]+ 521.2. 1H NMR (DMSO, 400 MHz): δ 11.75 (s, 1H); 9.13 (s, 1 H); 8.81 (s, 1 H); 7.71 (t, J=2.7 Hz, 1 H); 7.45 (s, 1 H); 7.40-7.37 (m, 1 H); 7.07 (d, J=3.5 Hz, 1 H); 6.95 (d, J=3.5 Hz, 1 H); 4.01 (t, J=4.6 Hz, 4 H); 3.87 (s, 2 H); 3.83 (t, J=4.6 Hz, 4 H); 2.58 (s, 4 H); 2.49 (s, 4 H); 1.10 (s, 6 H)

Provenance & Evidence