(2S)-N-(2,6-dimethylphenyl)-1,2,3,4-tetrahydro-2-pyridinecarboxamide -Drug Synthesis Database

【结构式】

【分子编号】19511

【品名】(2S)-N-(2,6-dimethylphenyl)-1,2,3,4-tetrahydro-2-pyridinecarboxamide

【CA登记号】

【分子式】C₁₄H₁₈N₂O

【分子量】230.3098

【元素组成】C 73.01% H 7.88% N 12.16% O 6.95%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(XV)

Compound (XII) is protected with benzyl chloroformiate (VII) to afford compound (XIII), which is condensed with 2,5-dimethylaniline (XIV) by means SOCl2/DMAP to yield amide (XIV). This compound (XIV) is deprotected by means trimethylsillyl chloride to yield compound (XV), which is hydrogenated by means Rh/Al2O3. Finally, this compound (V) is alkylated with 1-iodopropane by means potassium carbonate (K2CO3) to yield Ropivacaine.

参考文献中间体

合成目标

【1】 T. af Ekenstam, B.; Bovin, C. (Alpharma Inc.); L-N-n-Propylpipecolic acid-2,6-xylidide and method for preparing the same. JP 1985502054; WO 8500599 .
【2】 Sandeberg, R.V. (AstraZeneca plc); S-(-)-1-propyl-2',6'-pipecoloxylidide hydrochloride monohydrate, process for its preparation and pharmaceutical preparation containing it. EP 0239710; US 4870086 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	28758	1-iodopropane	107-08-4	C₃H₇I	详情	详情
(IV)	17527	2,6-Xylidine; 2,6-Dimethylaniline; 2,6-Dimethylphenylamine	87-62-7	C₈H₁₁N	详情	详情
(V)	17531	(2S)-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide		C₁₄H₂₀N₂O	详情	详情
(VII)	10101	Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene	501-53-1	C₈H₇ClO₂	详情	详情
(XII)	19508	(2S)-1,2,3,4-tetrahydro-2-pyridinecarboxylic acid		C₆H₉NO₂	详情	详情
(XIII)	19509	(2S)-1-[(benzyloxy)carbonyl]-1,2,3,4-tetrahydro-2-pyridinecarboxylic acid		C₁₄H₁₅NO₄	详情	详情
(XIV)	19510	benzyl (2S)-2-[(2,6-dimethylanilino)carbonyl]-3,4-dihydro-1(2H)-pyridinecarboxylate		C₂₂H₂₄N₂O₃	详情	详情
(XV)	19511	(2S)-N-(2,6-dimethylphenyl)-1,2,3,4-tetrahydro-2-pyridinecarboxamide		C₁₄H₁₈N₂O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XV)

3) The protection of 1,2,3,6-tetrahydropyridine-2(S)-carboxylic acid (XII) with benzyl chloroformate (VII) gives the benzyloxycarbonyl derivative (XIII), which is condensed with 2,6-xylidine (IV) with SOCl2 and DMAP as before yielding the amide (XIV). Deprotection of (XIV) with iodotrimethylsilane in dichloromethane affords N-(2,6-dimethylphenyl)-1,2,3,6-tetrahydropyridine-2(S)-carboxamide (XV), which is reduced with H2 over Rh/Al2O3 in DMF giving the saturated amide (V). Finally, this compound is alkylated with propyl iodide and K2CO3 as before.

参考文献中间体

合成目标

【1】 Prous, J.; Castaner, J.; ROPIVACAINE HYDROCHLORIDE < Rec INNM >. Drugs Fut 1989, 14, 8, 767.
【2】 Gawell, L.; Synthesis of tritium labelled ropivacaine - A new potential local anaesthetic. J Label Compd Radiopharm 1987, 24, 5, 521.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	17527	2,6-Xylidine; 2,6-Dimethylaniline; 2,6-Dimethylphenylamine	87-62-7	C₈H₁₁N	详情	详情
(V)	17531	(2S)-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide		C₁₄H₂₀N₂O	详情	详情
(VI)	19502	Propyl bromide; 1-Bromopropane	106-94-5	C₃H₇Br	详情	详情
(VII)	10101	Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene	501-53-1	C₈H₇ClO₂	详情	详情
(XII)	19508	(2S)-1,2,3,4-tetrahydro-2-pyridinecarboxylic acid		C₆H₉NO₂	详情	详情
(XIII)	19509	(2S)-1-[(benzyloxy)carbonyl]-1,2,3,4-tetrahydro-2-pyridinecarboxylic acid		C₁₄H₁₅NO₄	详情	详情
(XIV)	19510	benzyl (2S)-2-[(2,6-dimethylanilino)carbonyl]-3,4-dihydro-1(2H)-pyridinecarboxylate		C₂₂H₂₄N₂O₃	详情	详情
(XV)	19511	(2S)-N-(2,6-dimethylphenyl)-1,2,3,4-tetrahydro-2-pyridinecarboxamide		C₁₄H₁₈N₂O	详情	详情

Extended Information