4-Bromo-1H-pyrrolo(2,3-c)pyridine → 2-methyl-2-(4-((7-morpholino-5-(1H-pyrrolo[2,3-c]pyridin-4-yl)thiazolo[5,4-d]pyrimidin-2-yl)methyl)piperazin-1-yl)propanamide

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-[4-(7-morpholin-4-yl-5-(tributylstannanyl)thiazolo[5,4-d]pyrimidin-2-ylmethyl)piperazin-1-yl]isobutyramide (167 mg, 0.24 mmol), 4-bromo-1H-pyrrolo[2,3-c]pyridine (62 mg, 0.31 mmol), tetrakis(triphenylphosphine)palladium (28 mg, 10 mol %) and CuI (55 mg, 0.28 mmol) in dioxane (2.5 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 15:85) to give 131 as an pale yellow solid (12 mg, 10%). LCMS (Method F): RT 4.70 min, [M+H]+ 522.2. 1H NMR (DMSO, 400 MHz): δ 11.94 (s, 1H); 9.10 (s, 1 H); 8.88 (s, 1 H); 7.82 (s, 1 H); 7.35 (s, 1 H); 7.15 (s, 1 H); 7.04 (s, 1 H); 4.37 (s, 4 H); 3.95 (s, 2 H); 3.82 (t, J=4.6 Hz, 4 H); 2.68 (s, 4 H); 2.56 (s, 4 H); 1.13 (s, 6H)

Provenance & Evidence