2-[4-(4-Morpholin-4-yl-2-(tributylstannanyl)-thieno[3,2-d]pyrimidin-6-ylmethyl)piperazin-1-yl]isobutyramide → 2-(4-((2-(Imidazo[1,5-a]pyridin-8-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)-2-methylpropanamide

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 (132 mg, 0.19 mmol), 8-bromoimidazo[1,5-a]pyridine (45 mg, 0.23 mmol), Pd(PPh3)4 (22 mg, 0.02 mmol) and copper(I) thiophene-2-carboxylate (7 mg, 0.04 mmol) in dioxane (2 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 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 202 as a yellow solid (72 mg, 73%). LCMS (Method G): RT 5.12 min; [M+H]+ 521. 1H NMR (400 MHz, CHCl3-d): δ 8.33 (s, 1 H); 8.21 (s, 1 H); 8.04 (d, J=6.9 Hz, 1 H); 7.93 (d, J=6.9 Hz, 1 H); 7.36 (s, 1 H); 7.07 (m, 1 H); 6.74-6.69 (m, 1 H); 5.19 (s, 1 H); 4.07 (t, J=4.7 Hz, 4 H); 3.96-3.86 (m, 4 H); 3.88-3.83 (m, 2 H); 2.61 (s, 8 H); 1.25 (s, 6 H)

Provenance & Evidence