ethyl nicotinate -Drug Synthesis Database

【结构式】

【分子编号】23226

【品名】ethyl nicotinate

【CA登记号】614-18-6

【分子式】C₈H₉NO₂

【分子量】151.165

【元素组成】C 63.56% H 6% N 9.27% O 21.17%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(XI)

Condensation of ethyl nicotinate (XI) with 3-chlorophenylacetonitrile (XII) by means of sodium ethoxide in ethanol gives 2-(3-chlorophenyl)-3-oxo-3-(3-pyridyl)propionitrile (XIII), which by refluxing with concentrated HBr yields 2-(3-chlorophenyl)-1-(3-pyridyl)ethanone (XIV). The reduction of (XIV) with hydrazine hydrate and NaOH in diethylene glycol at 235-40 C affords 3-(2-phenylethyl) pyridine (XV), which is oxidized with H2O2 in hot acetic acid to provide the corresponding N-oxide (XVI). Reaction of (XVI) with NaCN and dimethyl sulfate in water affords the previously described 3-(2-phenylethyl)pyridine-2-carbonitrile (V), which can be worked up as previously described or cyclized with polyphosphoric acid (PPA) at 180 C to give 8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-one (XVII). The condensation of (XVII) with 1-methylpiperidin-4-ylmagnesium chloride (VI) in THF yields the corresponding carbinol (XVIII), which is dehydrated with PPA at 170 C to afford the previously reported 8-chloro-11-(1-methylpiperidin-4-ylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine (VIII).

参考文献中间体

合成目标

【1】 Castaner, J.; Leeson, P.; Graul, A.; Desloratadine. Drugs Fut 2000, 25, 4, 339.
【2】 Villani, F.J. (Schering Corp.); Novel aza-dibenzo[a,d]cycloheptene derivatives. US 3326924 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(V)	20644	3-(3-chlorophenethyl)-2-pyridinecarbonitrile		C₁₄H₁₁ClN₂	详情	详情
(VI)	20645	chloro(1-methyl-4-piperidinyl)magnesium		C₆H₁₂ClMgN	详情	详情
(VIII)	20647	8-chloro-11-(1-methyl-4-piperidinylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine	38092-89-6	C₂₀H₂₁ClN₂	详情	详情
(XI)	23226	ethyl nicotinate	614-18-6	C₈H₉NO₂	详情	详情
(XII)	34057	2-(3-chlorophenyl)acetonitrile; 3-chlorophenylacetonitrile	1529-41-5	C₈H₆ClN	详情	详情
(XIII)	34058	2-(3-chlorophenyl)-3-oxo-3-(3-pyridinyl)propanenitrile		C₁₄H₉ClN₂O	详情	详情
(XIV)	34059	2-(3-chlorophenyl)-1-(3-pyridinyl)-1-ethanone		C₁₃H₁₀ClNO	详情	详情
(XV)	34060	3-(3-chlorophenethyl)pyridine		C₁₃H₁₂ClN	详情	详情
(XVI)	34061	3-(3-chlorophenethyl)-1-pyridiniumolate		C₁₃H₁₂ClNO	详情	详情
(XVII)	16504	8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-one; 8-Chloro-10,11-dihydro-4-aza-5H-dibenzo[a,d]cycloheptan-5-one	31251-41-9	C₁₄H₁₀ClNO	详情	详情
(XVIII)	23553	8-chloro-11-(1-methyl-4-piperidinyl)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ol		C₂₀H₂₃ClN₂O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Claisen condensation of ethyl acetoacetate (I) with ethyl nicotinate (II) using 2.5 equivalents of LDA produced the corresponding diketoester, which was isolated as the enol form (III). Subsequent cyclization of (III) at 150 C with removal of EtOH under reduced pressure afforded pyrone (IV). This was finally coupled with 1-cyclohexene-carboxaldehyde (V) in the presence of L-proline to give the target pyranochromene.

参考文献中间体

合成目标

【1】 Hua, D.H.; et al.; A one-pot condensation of pyrones and enals. Synth. J Org Chem 1997, 62, 20, 6888.
【2】 Perchellet, J.-P.; Hua, D.H. (Kansas State University); Tricyclic and tetracyclic pyrones. US 5958970 .

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)	11819	ethyl acetoacetate; ethyl 3-oxobutanoate；Acetoacetic ester;Ethyl beta-ketobutyrate;ethyl 3-oxobutyrate	141-97-9	C₆H₁₀O₃	详情	详情
(II)	23226	ethyl nicotinate	614-18-6	C₈H₉NO₂	详情	详情
(III)	23227	ethyl (Z)-5-hydroxy-3-oxo-5-(3-pyridinyl)-4-pentenoate		C₁₂H₁₃NO₄	详情	详情
(IV)	23228	4-hydroxy-6-(3-pyridinyl)-2H-pyran-2-one		C₁₀H₇NO₃	详情	详情
(V)	23229	1-cyclohexene-1-carbaldehyde	1192-88-7	C₇H₁₀O	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

Claisen condensation of ethyl acetoacetate (I) with ethyl nicotinate (II) using 2.5 equivalents of LDA produced the corresponding diketoester, which was isolated as the enol form (III). Subsequent cyclization of (III) at 150 C with removal of EtOH under reduced pressure afforded pyrone (IV). This was finally coupled with (S)-perillaldehyde (V) in the presence of L-proline to give the target pyranochromene.

参考文献中间体

合成目标

【1】 Hua, D.H.; et al.; A one-pot condensation of pyrones and enals. Synth. J Org Chem 1997, 62, 20, 6888.

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)	11819	ethyl acetoacetate; ethyl 3-oxobutanoate；Acetoacetic ester;Ethyl beta-ketobutyrate;ethyl 3-oxobutyrate	141-97-9	C₆H₁₀O₃	详情	详情
(II)	23226	ethyl nicotinate	614-18-6	C₈H₉NO₂	详情	详情
(III)	23227	ethyl (Z)-5-hydroxy-3-oxo-5-(3-pyridinyl)-4-pentenoate		C₁₂H₁₃NO₄	详情	详情
(IV)	23228	4-hydroxy-6-(3-pyridinyl)-2H-pyran-2-one		C₁₀H₇NO₃	详情	详情
(V)	23230	(4S)-4-isopropenyl-1-cyclohexene-1-carbaldehyde	18031-40-8	C₁₀H₁₄O	详情	详情

Extended Information