2-[4-(4-Morpholin-4-yl-2-(tributylstannanyl)-thieno[3,2-d]pyrimidin-6-ylmethyl)piperazin-1-yl]isobutyramide → HCID 49834218, compound

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 (150 mg, 0.22 mmol), 1-benzenesulfonyl-4-bromo-1H-pyrrolo[3,2-c]pyridine (90 mg, 0.27 mmol), Pd(PPh3)4 (25 mg, 10 mol %) and CuI (50 mg, 0.25 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. The resulting residue was dissolved in IMS/dioxane (1:1 mL) and 12.5 M aqueous NaOH solution (0.1 mL) added. After stirring for 1 h 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 flash chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 05:95) to give 106 (28 mg, 24%) as a pale yellow solid. LCMS (Method F) RT 4.86 min; [M+H]+ 521.3. 1H NMR (CDCl3, 400 MHz): δ 9.11 (s, 1 H); 8.54 (d, J=5.6 Hz, 1 H); 7.45 (s, 1 H); 7.41 (dd, J=3.3, 0.9 Hz, 1 H); 7.38 (dd, J=5.6, 0.95 Hz, 1 H); 7.36 (d, J=3.3 Hz, 1 H); 7.10 (d, J=5.3 Hz, 1 H); 5.25 (d, J=5.2 Hz, 1 H); 4.10 (t, J=4.75 Hz, 4 H); 3.91 (t, J=4.7 Hz, 4 H); 3.85 (s, 2 H); 2.60 (s, 8 H); 1.24 (s, 6 H)

Provenance & Evidence