tert-butyl 2-(dimethylcarbamoyl)piperazine-1-carboxylate

反应条件: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Tert-butyl (3-bromo-2-chloro-5-cyanophenyl)carbamate (834 mg, 2.52 mmol), tert-butyl 2-(dimethylcarbamoyl)piperazine-1-carboxylate (647 mg, 2.52 mmol), Pd2(dba)3 (230 mg, 0.252 mmol), BINAP (157 mg, 0.252 mmol), Cs2CO3 (1229 mg, 3.77 mmol), and toluene (20 mL) were combined in a 250 ml flask. The flask was evacuated and backfilled with N2 3×, and the reaction was heated at 105° C. for 12 h. LCMS indicated SM was still present, so an additional 0.1 eq. each of catalyst and ligand were added, and the reaction was again purged with N2 and heated at 105° C. for 13 h. An additional 0.1 eq. each of catalyst and ligand were added, and the reaction was again purged with N2 and heated at 105° C. for 2 h. The reaction was cooled to room temperature and diluted with EtOAc. The solution was filtered through celite and the filtrate concentrated in vacuo. The crude material was purified by flash column chromatography (0-50% EtOAc/Hex; 120 g column). Tert-butyl 4-(3-((tert-butoxycarbonyl)amino)-2-chloro-5-cyanophenyl)-2-(dimethylcarbamoyl)piperazine-1-carboxylate (450 mg) was obtained as an orange glass. The flask was evacuated the reaction was again purged with N2 heated at 105° C. for 13 h the reaction was again purged with N2 heated at 105° C. for 2 h The reaction was cooled to room temperature diluted with EtOAc The solution was filtered through celite the filtrate concentrated in vacuo The crude material was purified by flash column chromatography (0-50% EtOAc/Hex; 120 g column)

反应条件: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Tert-butyl (3-bromo-2-chloro-5-cyanophenyl)carbamate (834 mg, 2.52 mmol), tert-butyl 2-(dimethylcarbamoyl)piperazine-1-carboxylate (647 mg, 2.52 mmol), Pd2(dba)3 (230 mg, 0.252 mmol), BINAP (157 mg, 0.252 mmol), Cs2CO3 (1229 mg, 3.77 mmol), and toluene (20 mL) were combined in a 250 ml flask. The flask was evacuated and backfilled with N2 3×, and the reaction was heated at 105° C. for 12 h. LCMS indicated SM was still present, so an additional 0.1 eq. each of catalyst and ligand were added, and the reaction was again purged with N2 and heated at 105° C. for 13 h. An additional 0.1 eq. each of catalyst and ligand were added, and the reaction was again purged with N2 and heated at 105° C. for 2 h. The reaction was cooled to room temperature and diluted with EtOAc. The solution was filtered through celite and the filtrate concentrated in vacuo. The crude material was purified by flash column chromatography (0-50% EtOAc/Hex; 120 g column). Tert-butyl 4-(3-((tert-butoxycarbonyl)amino)-2-chloro-5-cyanophenyl)-2-(dimethylcarbamoyl)piperazine-1-carboxylate (450 mg) was obtained as an orange glass. The flask was evacuated the reaction was again purged with N2 heated at 105° C. for 13 h the reaction was again purged with N2 heated at 105° C. for 2 h The reaction was cooled to room temperature diluted with EtOAc The solution was filtered through celite the filtrate concentrated in vacuo The crude material was purified by flash column chromatography (0-50% EtOAc/Hex; 120 g column)

反应条件: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Tert-butyl (3-bromo-2-chloro-5-cyanophenyl)carbamate (834 mg, 2.52 mmol), tert-butyl 2-(dimethylcarbamoyl)piperazine-1-carboxylate (647 mg, 2.52 mmol), Pd2(dba)3 (230 mg, 0.252 mmol), BINAP (157 mg, 0.252 mmol), Cs2CO3 (1229 mg, 3.77 mmol), and toluene (20 mL) were combined in a 250 ml flask. The flask was evacuated and backfilled with N2 3×, and the reaction was heated at 105° C. for 12 h. LCMS indicated SM was still present, so an additional 0.1 eq. each of catalyst and ligand were added, and the reaction was again purged with N2 and heated at 105° C. for 13 h. An additional 0.1 eq. each of catalyst and ligand were added, and the reaction was again purged with N2 and heated at 105° C. for 2 h. The reaction was cooled to room temperature and diluted with EtOAc. The solution was filtered through celite and the filtrate concentrated in vacuo. The crude material was purified by flash column chromatography (0-50% EtOAc/Hex; 120 g column). Tert-butyl 4-(3-((tert-butoxycarbonyl)amino)-2-chloro-5-cyanophenyl)-2-(dimethylcarbamoyl)piperazine-1-carboxylate (450 mg) was obtained as an orange glass. The flask was evacuated the reaction was again purged with N2 heated at 105° C. for 13 h the reaction was again purged with N2 heated at 105° C. for 2 h The reaction was cooled to room temperature diluted with EtOAc The solution was filtered through celite the filtrate concentrated in vacuo The crude material was purified by flash column chromatography (0-50% EtOAc/Hex; 120 g column)