4-Methylmorpholine → (4-Isopropyl-piperazin-1-yl)-(5-piperidin-1-ylmethyl-pyridin-2-yl)-methanone

関与物質

役割	名称	HCID	仕込み量
反応物	4-Methylmorpholine	HCID 7972	—
反応物	5-(Methoxycarbonyl)pyridine-2-carboxylic acid	HCID 314992	—
反応物	1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride	HCID 2723939	—
反応物	1-Hydroxybenzotriazole hydrate	HCID 2796029	—
反応物	1-Isopropylpiperazine dihydrochloride	HCID 12268378	—
反応物	6-(4-Isopropyl-piperazine-1-carbonyl)-nicotinic acid methyl ester	HCID 44515774	—
溶媒	Dichloromethane	HCID 6344	—
生成物	Ammonia	HCID 222	2%
生成物	(4-Isopropyl-piperazin-1-yl)-(5-piperidin-1-ylmethyl-pyridin-2-yl)-methanone	HCID 25126154	74%

反応手順

6-(4-Isopropyl-piperazine-1-carbonyl)-nicotinic acid methyl ester. To a solution of pyridine-2,5-dicarboxylic acid 5-methyl ester (1.00 g, 5.50 mmol) and 1-isopropyl-piperazine dihydrochloride (1.20 g, 6.10 mmol) in DCM (100 mL) was added 1-hydroxybenzotriazole hydrate (HOBt, 1.10 g, 8.30 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (EDC, 1.60 g, 8.30 mmol), and N-methyl morpholine (2.9 mL, 27.0 mmol). After 18 h, the reaction mixture was quenched with 1 N aq. NaHCO3 (50 mL) and extracted with DCM (3×50 mL). The organic layers were combined, dried (Na2SO4), and concentrated. Chromatography of the residue (SiO2; 2-5% 2 M NH3 in MeOH/DCM) gave the title compound (1.20 g, 74%).

情報源と証拠

DOI	10.6084/m9.figshare.5104873.v1
特許番号	US07947718B2
出典データセット	uspto-grants-2011_05
ORD ID	ord-d3e3bf082b0746e98c813168336111a5
出典メモ	uspto-grants-2011_05