Synthesis
(1) Preparation of tert-butyl 4-(pyrimidin-5-yl)piperazine-1-carboxylate: a 100 mL aubergine flask was charged with 5-bromopyrimidine (3.16 g, 20 mmol), N-BOC-piperazine (3.72 g, 20 mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP, 2.49 g, 4 mmol), cesium carbonate ( 13.0 g, 40 mmol) and tris(dibenzylideneacetone)dipalladium (Pd2(dba)3, 1.83 g, 2 mmol). Toluene (80 mL) was then added as solvent. The reaction mixture was heated to 90 °C and stirred for 12 h under the protection of nitrogen atmosphere. Upon completion of the reaction, the mixture was filtrated and the filtrate was concentrated under reduced pressure to remove the solvent. The crude product was purified by silica gel column chromatography with the eluent ratio of dichloromethane:methanol=50:1, and tert-butyl 4-(pyrimidin-5-yl)piperazine-1-carboxylate (3.1 g, 58.7% yield) was finally obtained.
References
[1] Tetrahedron Letters, 2006, vol. 47, # 15, p. 2549 - 2552
[2] Patent: EP3091008, 2016, A1. Location in patent: Paragraph 0380; 0381
[3] Patent: US2005/176722, 2005, A1. Location in patent: Page/Page column 20
