diethyl 3,6-dihydro-1,4(2H)-pyridinedicarboxylate -Drug Synthesis Database

【结构式】

【分子编号】43674

【品名】diethyl 3,6-dihydro-1,4(2H)-pyridinedicarboxylate

【CA登记号】

【分子式】C₁₁H₁₇NO₄

【分子量】227.26032

【元素组成】C 58.14% H 7.54% N 6.16% O 28.16%

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：(V)

The methylation of pyridine-4-carboxylic acid (X) gives the pyridinium iodide (XI), which is reduced with NaBH4 to yield 1-methyl-1,2,3,6-tetrahydropyridine-4-carboxylic acid ethyl ester (XII). The desmethylation of (XII) with ethyl chloroformate (XIII) affords 1,23,6-tetrahydropyridine-1,4-dicarboxylic acid diethyl ester (XIV), which is finally hydrolyzed and monodecarboxylated with HCl and TEA.

参考文献中间体

合成目标

【1】 Christensen, V.; Krogsgaard-Larsen, P.; Falch, E.; Chemistry and pharmacology of the GABA agonists THIP (Gabodaxol) and isoguvacine. Drugs Fut 1984, 9, 8, 597.
【2】 Johnston, G.A.R.; Krogsgaard-Larsen, P.; Structure-activity studies on the inhibition of GABA binding to rat brain membranes by muscinol and related compounds. J Neurochem 1978, 30, 1377-1382.
【3】 Krogsgaard-Larsen, P.; Christensen, T.R.; GABA agonists. Synthesis and structure-activity studies on analogues of isoguvacine and THIP. Eur J Med Chem 1979, 14, 157-164.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	43671	ethyl isonicotinate	1570-45-2	C₈H₉NO₂	详情	详情
(II)	43672	4-(ethoxycarbonyl)-1-methylpyridinium iodide		C₉H₁₂INO₂	详情	详情
(III)	43673	ethyl 1-methyl-1,2,3,6-tetrahydro-4-pyridinecarboxylate		C₉H₁₅NO₂	详情	详情
(IV)	11229	1-[(Chlorocarbonyl)oxy]ethane;ethyl carbonochloridate; Carbonchloridic acid ethyl ester;Ethyl chloroformate;Ethyl chlorocarbonate	541-41-3	C₃H₅ClO₂	详情	详情
(V)	43674	diethyl 3,6-dihydro-1,4(2H)-pyridinedicarboxylate		C₁₁H₁₇NO₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The preparation of the intermediate 1,2,3,6-tetrahydropyridine-4-carboxamide (VI) is illustrated in Scheme 1. Demethylation of tetrahydropyridine (I) with ethyl chloroformate in refluxing benzene affords carbamate (II), which is further hydrolyzed to the aminoacid (III) upon heating with concentrated HBr. Subsequent protection of (III) by means of di-t-butyl dicarbonate leads to N-Boc tetrahydropyridine-4-carboxylic acid (IV). Coupling of acid (IV) with ammonia in the presence of EDC/HOBt provides amide (V). The N-Boc protecting group of (V) is then removed with trifluoroacetic acid in CHCl3, yielding tetrahydropyridine (VI)

参考文献中间体

合成目标

【1】 Tomisawa, K.; Kumagai, T.; Nakazato, A.; Okubo, T. (Taisho Pharmaceutical Co., Ltd.); Carbamoyl tetrahydropyridine derivs.. EP 1176146 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	43676	methyl 10-[(hydroxyamino)carbonyl]-1,4-dioxa-7-azaspiro[4.5]decane-7-carboxylate	C₁₀H₁₆N₂O₆	详情	详情
(II)	43674	diethyl 3,6-dihydro-1,4(2H)-pyridinedicarboxylate	C₁₁H₁₇NO₄	详情	详情
(III)	62072	1,2,3,6-tetrahydro-4-pyridinecarboxylic acid	C₆H₉NO₂	详情	详情
(IV)	62073	1-(tert-butoxycarbonyl)-1,2,3,6-tetrahydro-4-pyridinecarboxylic acid	C₁₁H₁₇NO₄	详情	详情
(V)	62074	tert-butyl 4-(aminocarbonyl)-3,6-dihydro-1(2H)-pyridinecarboxylate	C₁₁H₁₈N₂O₃	详情	详情
(VI)	60299	1,2,3,6-tetrahydro-4-pyridinecarboxamide	C₆H₁₀N₂O	详情	详情

Extended Information