Synthetic Route of 3718-04-5, These common heterocyclic compound, 3718-04-5, name is 5-Vinyl-1H-imidazole, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
Example 20 (E)-2-(4-fluorophenyl)- 1 -methyl- 1 -(4-(2-(l -methyl- 1 H-imidazol-4-yl)vinyl)phenyl)- 1.2.3.4- tetrahvdroisoquinolin-6-ol and (EN)-2-(4-fluorophenvn-l-methyl-l-(4-(2-(l -methyl-lH-imidazol- 5-yl)vinyl)phenyl)-1.2.3.4-tetrahvdroisoquinolin-6-ol To a 30 mL vial, 4-vinyl-lH-imidazole (357 mg, 3.79 mmol) was dissolved in tetrahydrofuran (2 mL) and the solution was cooled to 0C. Sodium hydride (60% dispersion in mineral oil, 152 mg, 3.79 mmol) was added and the mixture was stirred for 10 min at 0C. The reaction mixture was charged with iodomethane (237 mu^, 3.79 mmol) and stirred overnight at room temperature. The reaction was quenched with saturated ammonium chloride (15 mL) and dichloromethane (25 mL) was added. The organic phase was collected, passed through a phase separator and concentrated to give crude product. Crude material was purified by silica gel chromatography (0-20% methanol/dichloromethane) to afford a mixture of 1 -methyl -4-vinyl-lH- imidazole and l-methyl-5 -vinyl- lH-imidazole (290 mg, 71% yield) as a yellow oil. NMR (400 MHz, CHLOROFORM-^ delta 3.51 (s, 3 H), 3.49 (s, 3 H), 4.97 (dd, J=11.12, 1.52 Hz, 1 H), 5.09 (dd, J=11.12, 1.01 Hz, 1 H), 5.44 (dd, J=17.68, 1.01 Hz, 1 H), 5.67 (dd, J=17.43, 1.77 Hz, 1 H), 6.25 – 6.49 (m, 2 H), 6.62 – 6.73 (m, 1 H), 7.04 (s, 1 H), 7.25 (d, J=7.58 Hz, 2 H). To a 5 mL microwave vial, l-(4-bromophenyl)-2-(4-fluorophenyl)-l-methyl- l,2,3,4-tetrahydroisoquinolin-6-ol (Intermediate Ml) (100 mg, 0.243 mmol) was dissolved in dimethylformamide (1.617 mL) and triethylamine (169 mu^, 1.213 mmol) was added. The vial was charged with a mixture of l-methyl-4 -vinyl- lH-imidazole and 1 -methyl-5 -vinyl- 1H- imidazole (1.455 mL, 0.728 mmol) and Pd(PPh3)2Cl2 (26 mg, 0.036 mmol). The system was flushed with nitrogen and heated at 150 C for 1 h under microwave radiation. The mixture was cooled to room temperature and quenched with saturated ammonium chloride. The reaction mixture was extracted three times with dichloromethane, the organic layers were combined, passed through a phase separator and concentrated to give crude material. The crude material was purified on an achiral C4 waters Atlantis Hilic 19 x 150mm 5um column with a mobile phase of 5-10% methanol with 10 mM ammonium hydroxide at a flow rate of 80 g/min to obtain (E)-2-(4- fluorophenyl)- 1 -methyl- 1 -(4-(2-( 1 -methyl- 1 H-imidazol-4-yl)vinyl)phenyl)- 1 ,2,3 ,4- tetrahydroisoquinolin-6-ol (2.4 mg, 2% yield) as a yellow solid and (E)-2-(4-fluorophenyl)-l- methyl-l-(4-(2-(l -methyl- lH-imidazol-5-yl)vinyl)phenyl)-l, 2,3 ,4-tetrahydroisoquinolin-6-ol (4 mg, 3% yield) as a white solid.
The synthetic route of 3718-04-5 has been constantly updated, and we look forward to future research findings.