Pyridine → 4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid [4-tert-butylsulfamoyl-2-(4,4-dimethyl-cyclohex-1-enyl)-phenyl]-amide

Participants

Reaction Steps

A solution of 300 mg (0.976 mmol) of 4-amino-3-bromo-N-tert-butyl-benzenesulfonamide (as prepared in Example 48, step (a)) in toluene (8 mL) and EtOH (4 mL) was treated with 253 mg (1.07 mmol) of 2-(4,4-dimethyl-cyclohex-1-enyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane and 3.90 mL (7.81 mmol) of 2.0 M Na2CO3. The mixture was degassed via sonication, placed under Ar, treated with 113 mg (0.0976 mmol) of Pd(PPh3)4, and heated to 80° C. for 6 h. The mixture was diluted with EtOAc (30 mL) and washed with water (2×20 mL). The organic layer was dried (MgSO4) and concentrated in vacuo. Silica gel chromatography of the residue on a 50-g Varian MegaBond Elut SPE column with 1-4% MeOH—CH2Cl2 afforded 158 mg (48%) of 4-amino-N-tert-butyl-3-(4,4-dimethyl-cyclohex-1-enyl)-benzenesulfonamide as a colorless glassy solid. A suspension of 215 mg (0.704 mmol) 4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylate potassium salt (as prepared in Example 11, step (d)) in CH2Cl2 (10 mL) was treated with 60.0 μL (0.704 mmol) of pyridine for 5 min. The mixture was then treated with 51.4 μL (0.704 mmol) of SOCl2 at RT for 30 min. A solution of 158 mg (0.0470 mmol) of 4-amino-N-tert-butyl-3-(4,4-dimethyl-cyclohex-1-enyl)-benzenesulfonamide (as prepared earlier in this step) in CH2Cl2 (5 mL) was treated with the acid chloride solution and stirred at RT for 17 h. The mixture was diluted with CH2Cl2 (30 mL) and washed with saturated aqueous NaHCO3 (1×20 mL). The organic layer was dried (MgSO4) and concentrated in vacuo. Silica gel chromatography of the residue on a 50-g Varian MegaBond Elut SPE column with 1% MeOH—CH2Cl2 afforded 100.0 mg (17%) of the title compound as a white solid: 1H-NMR (CDCl3; 400 MHz): δ 9.95 (br s, 1H), 8.55 (d, 1H, J=8.8 Hz), 7.78 (dd, 1H, J=8.8, 2.4 Hz), 7.78 (s, 1H), 7.69 (d, 1H, J=2.4 Hz), 5.92 (s, 2H), 5.84-5.80 (m, 1H), 4.55 (br s, 1H), 3.68-3.62 (m, 2H), 2.32-2.24 (m, 2H), 2.14-2.08 (m, 2H), 1.63-1.56 (m, 2H), 1.23 (s, 9H), 1.11 (s, 6H), 1.00-0.94 (m, 2H), 0.00 (s, 9H).

Provenance & Evidence