2-[4-(4-Morpholin-4-yl-2-(tributylstannanyl)-thieno[3,2-d]pyrimidin-6-ylmethyl)piperazin-1-yl]isobutyramide → 2-Methyl-2-(4-((2-(8-methylimidazo[1,2-a]pyridin-5-yl)-4-morpholinothieno[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-(tributylstannanyl)-thieno[3,2-d]pyrimidin-6-ylmethyl)piperazin-1-yl]isobutyramide (205 mg, 0.30 mmol), 5-bromo-8-methylimidazo[1,2-a]pyridine (75 mg, 0.35 mmol), Pd(PPh3)4 (34 mg, 0.03 mmol) and copper(I) thiophene-2-carboxylate (11 mg, 0.06 mmol) in dioxane (3 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 (10 g). The cartridge was washed with MeOH then the desired product was eluted with 2 M NH3 in MeOH. The resulting residue was purified by flash chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 10:90) to give a solid that was triturated in MeOH, filtered and dried at 60° C. under vacuum for 24 hours to give 201 as a white solid (97 mg, 62%). LCMS (Method G) RT 5.11 min; [M+H]+ 535. 1H NMR (400 MHz, CHCl3-d): δ 9.29 (s, 1 H); 7.93 (d, J=7.3 Hz, 1 H); 7.75 (s, 1 H); 7.37 (s, 1 H); 7.15 (d, J=7.3 Hz, 1 H); 7.13-6.96 (m, 1 H); 5.21 (s, 1 H); 4.06 (t, J=4.7 Hz, 4 H); 3.91 (t, J=4.7 Hz, 4 H); 3.86 (s, 2 H); 2.73 (s, 3 H); 2.62 (s, 8 H); 1.25 (s, 6 H)

Provenance & Evidence