2-Methyltetrahydrofuran → 5'-(5-Chloropyridin-3-yl)-4-methoxy-5''-methyldispiro[cyclohexane-1,2'-[1]benzofuran-3',2''-imidazol]-4''-amine

Participants

Reaction Conditions

Reaction Steps

Sodium tetrachloropalladate (II) (2.294 mg, 7.80 μmol), 3-(di-tert-butylphosphonium)propane sulfonate (4.19 mg, 0.02 mmol), 5-chloropyridin-3-ylboronic acid (25.8 mg, 0.16 mmol) and 5′-bromo-4-methoxy-5″-methyldispiro[cyclohexane-1,2′-[1]benzofuran-3′,2″-imidazol]-4″-amine (Example 29, 59 mg, 0.16 mmol), was added to a vial. 2-Methyl-tetrahydrofuran (1 mL) and 2 M aq. K2CO3 (0.234 mL, 0.47 mmol) was added and the mixture was degassed by bubbling nitrogen gas through the solution. The vial was sealed and heated in a microwave reactor at 90° C. for 30 min and the crude mixture was combined with a second reaction from 20 mg (0.05 mmol) of 5′-bromo-4-methoxy-5″-methyldispiro[cyclohexane-1,2′-[1]benzofuran-3′,2″-imidazol]-4″-amine. Water (5 mL) and EtOAc (5 mL) was added and the phases were separated. The aqueous phase was extracted with EtOAc (5 mL) and the combined organic layers were dried over MgSO4, filtered and evaporated. Purification by flash chromatography using a 0-10% gradient of MeOH, containing 1.2% 7M NH3 in MeOH, in DCM afforded 36 mg of the title compound (56% yield): 1H NMR (500 MHz, DMSO-d6) δ ppm 1.22 (m, 1 H), 1.46 (m, 3 H), 1.81 (m, 2 H), 1.97 (m, 2 H), 2.21 (s, 3 H), 3.10 (m, 1 H), 3.22 (s, 3 H), 6.71 (br. s., 2 H), 7.01 (m, 2 H), 7.61 (dd, 1 H), 8.08 (t, 1 H), 8.51 (d, 1 H), 8.72 (d, 1 H); MS (APCI+) m/z 411 [M+H]+.

Provenance & Evidence