Reaction Steps
Step 1: Sodium hydride (44 mg of 95%, 1.74 mmol) was added to an ice cold solution of methyl 3-cyclohexyl-2-(2-vinylphenyl) 1H-indole-6-carboxylate (0.500 mg, 1.34 mmol) in THF (6 mL). When the evolution of hydrogen subsided, 2,3-dibromoprop-1-ene (402 mg, 2.01 mmol) was added in a single portion. Stirring was continued at 0° C. for 2 hr and then at 22° C. for 24 hr. The solution was concentrated and the residue chromatographed on SiO2 with petroleum ether-ethyl acetate (10:1 H using the flash technique to afford methyl 1-(2-bromoallyl)-3-cyclohexyl-2-(2-vinylphenyl)-1H-indole-6-carboxylate (285 mg, 44.5%) as a gummy solid. MS m/z 479 (MH+). Step 2: Tetrakis(triphenylphosphine)palladium(0 H (38 mg, 0.033 mmol) was added to a stirred and degassed mixture of methyl 1-(2-bromoallyl)-3-cyclohexyl-2-(2-vinylphenyl)-1H-indole-6-carboxylate (157 mg, 0.33 mmol), 3-furylboronic acid (54.5 mg, 0.49 mmol), LiCl (55 mg, 0.66 mmol) in ethanol (2 mL) and toluene (2 mL) containing 1M aqueous sodium carbonate (0.82 mL, 0.82 mmol). The mixture was heated under reflux for 1 hr, cooled and partitioned between ethyl acetate and water. The organic layer was washed (water, brine), dried over sopdium sulfate and concentrated. The crude product was purified on a silicic acid thick layer plate. The plate was eluted with hexanes-ethyl acetate (10:1 H to provide methyl 3-cyclohexyl-1-(furan-3-yl)-2-(2-vinylphenyl)-1H-indole-6-carboxylate as a gum (57 mg, 37%). MS m/z 466 (MH+); 1H NMR (500 MHz, CHLOROFORM-D) δ ppm 1.15-1.89 (m, 10 H) 2.42-2.53 (m, 1 H) 3.91 (s, 3 H) 4.25 (s, 1 H) 4.48 (d, J=17.40 Hz, 1 H) 4.82 (d, J=17.40 Hz, 1 H) 4.82 (d, J=17.40 Hz, 1 H). 5.09-5.17 (m, 2 H) 5.69 (d, J=17.70 Hz, 1 H) 6.34-6.47 (m, 2 H) 7.18-7.23 (m, 2 H) 7.28 (t, J=7.93 Hz, 1 H) 7.32 (t, J=1.68 Hz, 1 H) 7.42 (t, J=7.63 Hz, 1 H) 7.69 (d, J=7.63 Hz, 1 H) 7.79-7.85 (m, 2 H) 8.00 (s, 1 H). Step 3: Grubb's second generation catalyst (10 mg) was added to a solution of methyl 3-cyclohexyl-1-(furan-3-yl)-2-(2-vinylphenyl)-1H-indole-6-carboxylate (47 mg) in methylene chloride (8 mL). The solution was stirred under reflux for 18 hr and concentrated to dryness The residue was purified on a silicic acid preparative plate. The plate was eluted with hexanes-ethyl acetate (10:1 H. The product containing band was extracted and the extract was concentrated. Purification on a second thick layer plate afforded 13-cyclohexyl-6-(furan-3-yl)-7H-indolo{2,1-a][2]benzazepine-10-carboxylate as a golden solid (17 mg, 39%). MS m/z 438 (MH+); 1H NMR (300 MHz, CHLOROFORM-D) δ ppm 1.11-2.16 (m, 10H) 2.78-2.95 (m, 1 H) 3.94 (s, 3 H) 4.34-4.49 (m, 1 H) 5.00-5.15 (m, 1 H) 6.60 (s, 1 H) 6.93 (s, 1 H) 7.38-7.45 (m, 4 H) 7.55 (d, J=8.42 Hz, 1 H) 7.70 (dd, J=8.42, 1.46 Hz, 1 H) 7.81-7.88 (m, 2 H) 8.17 (s, 1 H). Step 4: A mixture of the preceding ester (17 mg) in THF (250 μL), methanol (250 μL), and 1.0 N NaOH (200 μL) was heated at 100° C. on a microwave apparatus for 15 min. The resulting solution was cooled and acidified with dilute HCl to precipitate the titled acid as a golden solid. MS m/z 424 (MH+).
