p-Toluenesulfonic acid → 4-[2-((S)-1-tert-Butoxycarbonyl-piperidin-3-yloxy)-4-trifluoromethyl-phenylamino]-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylic acid methyl ester

関与物質

役割	名称	HCID	仕込み量
反応物	p-Toluenesulfonic acid	HCID 6101	—
反応物	Methyl 4-chloro-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylate	HCID 2759834	—
反応物	(S)-tert-butyl 3-(2-amino-5-(trifluoromethyl)phenoxy)piperidine-1-carboxylate	HCID 58413142	—
溶媒	Dichloromethane	HCID 6344	—
溶媒	Potassium Carbonate	HCID 11430	—
溶媒	1,4-Dioxane	HCID 31275	—
生成物	4-[2-((S)-1-tert-Butoxycarbonyl-piperidin-3-yloxy)-4-trifluoromethyl-phenylamino]-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylic acid methyl ester	HCID 58413022	—

反応条件

温度	80 °C

反応手順

4-Chloro-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylic acid methyl ester (326 mg) and (S)-tert-butyl 3-(2-amino-5-(trifluoromethyl)phenoxy)piperidine-1-carboxylate (485 mg) was dissolved in dioxane (4 ml), p-toluenesulfonic acid (26 mg) was added. The reaction mixture was heated at 80° C. for about 5 h. The mixture was diluted with dichloromethane and 10% aq. K2CO3 solution. The organic layer was separated, passed through a hydrophobic frit and concentrated in vacuo. The residue was purified by column chromatography (silica gel; solvent:100% iso hexane→4:1 H:E).

情報源と証拠

DOI	10.6084/m9.figshare.5104873.v1
特許番号	US08648068B2
出典データセット	uspto-grants-2014_02
ORD ID	ord-7bcf1c628de04fa0ac63805b61bfb936
出典メモ	uspto-grants-2014_02