Hydrochloric Acid → 1-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-piperidine-3-carboxylic acid

関与物質

役割	名称	HCID	仕込み量
反応物	Hydrochloric Acid	HCID 313	—
反応物	Nipecotic Acid	HCID 4498	—
反応物	Potassium Carbonate	HCID 11430	—
反応物	6-Chloro-N-[2-(2,4-dichlorophenyl)ethyl]-2-methoxy-4-pyrimidinamine	HCID 57636004	—
溶媒	Water	HCID 962	—
溶媒	N-methyl-2-pyrrolidone	HCID 13387	—
生成物	1-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-piperidine-3-carboxylic acid	HCID 11669053	47.4%

反応条件

温度	140 °C

反応手順

In a tube is combined (6-chloro-2-methoxy-pyrimidin-4-yl)-[2-(2,4-dichloro-phenyl)-ethyl]-amine [200 mg, 0.6 mmol, Intermediate (44)], nipecotic acid (194 mg, 1.5 mmol), K2CO3 (249 mg, 1.8 mmol) and 1-methyl-2-pyrrolidinone (2.5 mL). The tube is sealed and heated to 140° C. and stirred for hours. The mixture is allowed to cool to ambient temperature, stand for 12 hours, diluted with water (20 mL) and acidified using 3M HCl. A precipitate forms and is collected by filtration and dried under high vacuum to afford 1-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-piperidine-3-carboxylic acid [121 mg, 47%, Example 73] as a solid. LCMS RT=2.15 minutes, MS: 425 (M+H). IC50=0.8 nM

情報源と証拠

DOI	10.6084/m9.figshare.5104873.v1
特許番号	US08193183B2
出典データセット	uspto-grants-2012_06
ORD ID	ord-3b788c77b1ea46e3ae0a76f69167e7f9
出典メモ	uspto-grants-2012_06