Cesium carbonate → Tert-butyl 4-(3-((tert-butoxycarbonyl)amino)-2-chloro-5-cyanophenyl)-2-(dimethylcarbamoyl)piperazine-1-carboxylate

温度

105 °C

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.

1. customThe flask was evacuated
2. customthe reaction was again purged with N2
3. temperatureheated at 105° C. for 13 h
4. customthe reaction was again purged with N2
5. temperatureheated at 105° C. for 2 h
6. temperatureThe reaction was cooled to room temperature
7. additiondiluted with EtOAc
8. filtrationThe solution was filtered through celite
9. concentrationthe filtrate concentrated in vacuo
10. customThe crude material was purified by flash column chromatography (0-50% EtOAc/Hex; 120 g column)

ORDレコード

ord-bfe20390fcb34d299a5ed9ea02a36223

出典データセット

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09273057B2