2-[4-(4-Morpholin-4-yl-2-(tributylstannanyl)-thieno[3,2-d]pyrimidin-6-ylmethyl)piperazin-1-yl]isobutyramide → 2-Methyl-2-(4-((4-morpholino-2-(1h-pyrrolo[2,3-b]pyridin-4-yl)thieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)propanamide

Participants

Reaction Steps

A mixture of 2-[4-(4-morpholin-4-yl-2-(tributlystannanyl)thieno[3,2-d]pyrimidin-6-ylmethyl)piperazin-1-yl]isobutyramide (0.331 g, 0.48 mmol), 4-bromopyrrolo[2,3-b]pyridine-1-carboxylic acid tert-butylester (0.170 g, 0.573 mmol), Pd(Ph3)4 (55.1 mg, 0.048 mmol) and CuI (109 mg, 0.573 mmol) in toluene (8 mL) was purged with argon, then subjected to microwave irradiation at 140° C. for 20 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 the resulting solution 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 5:95) followed by reverse phase HPLC (Phenomenex Gemini 5u C18, 20 mM triethylamine in water on a gradient of acetonitrile 70:30 to 40:60) to give 695 as a white powder (0.049 g, 20%). LCMS (Method F): RT 5.07 min, [M+H]+ 521.3. 1H NMR (CDCl3, 400 MHz) δ 8.93 (s, 1 H); 8.43 (d, J=5.2 Hz, 1 H); 8.08 (d, J=5.2 Hz, 1 H); 7.43 (d, J=2.2 Hz, 2 H); 7.38 (s, 1 H); 7.09 (d, J=5.2 Hz, 1 H); 5.24 (d, J=5.2 Hz, 1 H); 4.10 (t, J=4.7 Hz, 4 H); 3.92 (t, J=4.7 Hz, 4 H); 3.86 (s, 2 H); 2.65-2.58 (m, 4 H); 1.60-1.55 (m, 4 H); 1.24 (s, 6 H)

Provenance & Evidence