{1-[2-(8-Benzyloxyimidazo[1,2-a]pyridin-5-yl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl]piperidin-4-yl}dimethylamine → 5-(6-((4-(Dimethylamino)piperidin-1-yl)methyl)-4-morpholinothieno[3,2-d]pyrimidin-2-yl)imidazo[1,2-a]pyridin-8-ol

Participants

Reaction Conditions

Reaction Steps

A mixture of {1-[2-(8-benzyloxyimidazo[1,2-a]pyridin-5-yl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl]piperidin-4-yl}dimethylamine (381 mg, 0.65 mmol) in TFA was heated at 140° C., for 10 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 appropriate fractions were combined and evaporated. The resulting residue was purified by reverse phase HPLC (Phenomenex Gemini 5u C18, 20 mM triethylamine in water on a gradient of acetonitrile 95:5 to 2:98) to give 689 as a yellow solid (32 mg, 10%). LCMS (Method F) RT 3.98 min; [M+H]+ 494. 1H NMR (400 MHz, CH3OH-d): δ 9.43 (d, J=1.6 Hz, 1 H); 8.04 (d, J=8.2 Hz, 1 H); 7.65 (d, J=1.6 Hz, 1 H); 7.34 (s, 1 H); 6.71 (d, J=8.2 Hz, 1 H); 4.03 (t, J=4.7 Hz, 4 H); 3.87 (m, 7 H); 3.07 (d, J=11.5 Hz, 2 H); 2.37 (s, 6 H); 2.34 (m, 1 H); 2.16 (t, J=11.5 Hz, 2 H); 1.91 (d, J=12.3 Hz, 2 H); 1.66-1.54 (m, 2 H)

Provenance & Evidence