Piperazine → 4-Piperazin-1-yl-1-tritylbenzimidazole

Participants

Reaction Conditions

Reaction Steps

A 2.0-5.0 mL microwave vial was charged with 4-bromo-1-trityl-1H-benzo[d]imidazole (300 mg, 0.68 mmol), Sodium tert- butoxide (92 mg, 0.96 mmol), rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (25.5 mg, 0.04 mmol), Piperazine (0.321 mL, 4.10 mmol) and toluene (5 mL). The reaction mixture was degassed for 10 minutes with nitrogen, and then Tris(dibenzylideneacetone)dipalladium(0)-chloroform adduct (14.14 mg, 0.01 mmol) was added. The reaction mixture was stirred at 90°C under microwave irradiation for 1h. The solution was diluted with EtOAc and washed with water, saturated NaHCO3 solution, brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced vacuum. The crude material was loaded on a 24g silica gel column and purified on a Teledyne Isco instrument, eluting with 10 : 1 / DCM : MeOH containing 0.2% ammonium hydroxide (v/v) to provide 4-(piperazin-1-yl)-1-trityl-1H-benzo[d]imidazole (130 mg, 42.8 %) as a solid. The product was analyzed by analytical HPLC MS using the high pH gradient method (mobile phase: 5-95% B; A: H2O with 10 mM NH5CO3 and 0.375% NH4OH v/v, B: MeOH, 2.25 min run) on X-Bridge C18, 2.1 x 30 mm, 5 mm particle size. MS _m/z_ 445.6 [M+H]\+ (ESI), Rt 2.61 min; 1H NMR (400 MHz, CHLOROFORM-d) d ppm 1.64 (br. s., 1 H), 3.11 - 3.22 (m, 4 H), 3.48 - 3.59 (m, 4 H), 6.08 (d, J=8.20 Hz, 1 H), 6.54 (d, J=7.42 Hz, 1 H), 6.79 (t, J=8.01 Hz, 1 H), 7.13 - 7.23 (m, 6 H), 7.30 (d, J=3.91 Hz, 9 H), 7.79 (s, 1 H).

Provenance & Evidence