Nitrogen → (2-methyl-1-{2-[5-(4-trimethylsilanylethynyl-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-propyl)-carbamic acid methyl ester

関与物質

役割	名称	HCID	仕込み量
反応物	Nitrogen	HCID 947	—
反応物	Triethylamine	HCID 8471	—
反応物	Trimethylsilylacetylene	HCID 66111	—
反応物	Methyl (1-(2-(4-(4-bromophenyl)-1H-imidazol-2-YL)pyrrolidin-1-YL)-3-methyl-1-oxobutan-2-YL)carbamate	HCID 66620141	—
触媒	Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)	HCID 24350	—
触媒	HCID 178418397	HCID 178418397	—
溶媒	Dimethylformamide	HCID 6228	—
生成物	(2-methyl-1-{2-[5-(4-trimethylsilanylethynyl-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-propyl)-carbamic acid methyl ester	HCID 66619941	59.5%

反応条件

温度	80 °C

反応手順

A solution of (1-{2-[5-(4-bromo-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (5.00 g, 11.1 mmol), TMS-acetylene (7.90 mL, 55.5 mmol) and triethylamine (4.64 mL, 33.3 mmol) in DMF (56 mL) was degassed with N2 gas for 20 minutes. To the degassed solution was added Pd(PPh3)4 (1.28 g, 1.11 mmol) and CuI (106 mg, 0.56 mmol). The pressure flask was sealed then heated at 80° C. overnight. After cooling to room temperature, the reaction was concentrated then diluted with EtOAc and washed with water. The aqueous phase was back-extracted two times then the organic phases were combined and dried over Na2SO4. After concentration, the crude material was purified by silica gel chromatography (10-80% EtOAc-hexanes gradient) to afford (2-methyl-1-{2-[5-(4-trimethylsilanylethynyl-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-propyl)-carbamic acid methyl ester (3.08 g, 6.60 mmol, 59% yield). LCMS-ESI+: calc'd for C25H35N4O3Si: 467.3 (M+H+). Found: 467.1 (M+H+).

情報源と証拠

DOI	10.6084/m9.figshare.5104873.v1
特許番号	US08841278B2
出典データセット	uspto-grants-2014_09
ORD ID	ord-ae3d8b72209c48d299799388703f3b88
出典メモ	uspto-grants-2014_09