2-methoxyisonicotinonitrile -Drug Synthesis Database

【结构式】

【分子编号】23943

【品名】2-methoxyisonicotinonitrile

【CA登记号】

【分子式】C₇H₆N₂O

【分子量】134.13752

【元素组成】C 62.68% H 4.51% N 20.88% O 11.93%

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：(II)

The reaction of 2-chloro-4-cyanopyridine (I) with sodium methoxide in refluxing methanol gives 2-methoxy-4-cyanopyridine (II), which by reduction with H2 over Raney-Ni and semicarbazide HCl in water-ethanol is converted to 2-methoxypyridine-4-carboxyaldehyde (III). The condensation of (III) with malonic acid (IV) by means of piperidine in hot pyridine yields 3-(2-methoxy-4-pyridyl)acrylic acid (V), which is esterified with ethanol and H2SO4 to the ethyl ester (VI). The reduction of (VII) with H2 over Pd/C in ethanol affords the corresponding propionate (VII). Formylation of (VII) with ethyl formate and NaH gives ethyl 2-formyl-3-(2-methoxy-4-pyridyl)propionate (VIII), which is cyclized with nitroguanidine (IX) by means of sodium methoxide in refluxing methanol yielding 2-nitroamino-5-12-methoxy-4-pyridylmethylpyrimidin-4(1H)-one (X). The reaction of (X) with 2-[5-(dimethylaminomethyl)-2 furylmethylthio]ethylamine in refluxing ethanol gives the O-methyl derivative of SK&F 93574 (XII), whicn is finally deprotected with HCl in refluxing ethanol.

参考文献中间体

合成目标

【1】 Brown, T.H.; Ife, R.J. (SmithKline Beecham plc); Pyrimidine compounds. DD 140252; EP 0003677; ES 477667; US 4234588; US 4649141 .
【2】 Adger, B.M.; Lewis, N.J. (SmithKline Beecham plc); Chemical process. EP 0141560 .
【3】 Prous, J.; Castaner, J.; SK&F-93574. Drugs Fut 1986, 11, 8, 671.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	23944	1-Hydrazinecarboxamide	563-41-7	CH₅N₃O	详情	详情
(I)	23940	2-Chloro-4-pyridinecarbonitrile; 2-chloroisonicotinonitrile	33252-30-1	C₆H₃ClN₂	详情	详情
(II)	23943	2-methoxyisonicotinonitrile		C₇H₆N₂O	详情	详情
(III)	23941	2-methoxyisonicotinaldehyde		C₇H₇NO₂	详情	详情
(IV)	12963	Malonic acid	141-82-2	C₃H₄O₄	详情	详情
(V)	23945	(Z)-3-(2-methoxy-4-pyridinyl)-2-propenoic acid		C₉H₉NO₃	详情	详情
(VI)	23946	ethyl (Z)-3-(2-methoxy-4-pyridinyl)-2-propenoate		C₁₁H₁₃NO₃	详情	详情
(VII)	23947	ethyl 3-(2-methoxy-4-pyridinyl)propanoate		C₁₁H₁₅NO₃	详情	详情
(VIII)	23948	ethyl 2-formyl-3-(2-methoxy-4-pyridinyl)propanoate		C₁₂H₁₅NO₄	详情	详情
(IX)	23949	N2-Nitroguanidine		CH₄N₄O₂	详情	详情
(X)	23950	5-(2-Methoxypyridin-4-yl)-2-(nitroamino)pyrimidin-4(1H)-one		C₁₁H₁₁N₅O₄	详情	详情
(XI)	13851	2-[([5-[(Dimethylamino)methyl]-2-furyl]methyl)sulfanyl]-1-ethanamine; N-[(5-[[(2-Aminoethyl)sulfanyl]methyl]-2-furyl)methyl]-N,N-dimethylamine		C₁₀H₁₈N₂OS	详情	详情
(XII)	23951	2-([2-[([5-[(dimethylamino)methyl]-2-furyl]methyl)sulfanyl]ethyl]amino)-5-[(2-methoxy-4-pyridinyl)methyl]-4(1H)-pyrimidinone		C₂₁H₂₇N₅O₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

Dichlorophenylpiperazine (III) was prepared from aniline (I) by dehydrative cyclization with diethanolamine (II) in the presence of P2O5 and Et3N-HCl at 200 C. Alkylation of piperazine (III) with N-(4-bromobutyl) phthalimide (IV) gave (V), and subsequent hydrazinolysis of the phthalimide provided the (4-aminobutyl)piperazine (VI). Finally, condensation of (VI) with biphenylene-2-carboxylic acid (VII) yielded the target amide.

参考文献中间体

合成目标

【1】 Yuan, J.; Chen, X.; Brodbeck, R.; Primus, R.; Braun, J.; Wasley, W.F.; Thurkauf, A.; NGB 2904 and NGB 2849: Two highly selective dopamine D3 receptor antagonists. Bioorg Med Chem Lett 1998, 8, 19, 2715.

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)	28562	2,3-dichlorophenylamine	608-27-5	C₆H₅Cl₂N	详情	详情
(II)	24273	2-[(2-hydroxyethyl)amino]-1-ethanol	111-42-2	C₄H₁₁NO₂	详情	详情
(III)	23943	2-methoxyisonicotinonitrile		C₇H₆N₂O	详情	详情
(IV)	17163	N-(4-Bromobutyl)phthalimide; 2-(4-Bromobutyl)-1H-isoindole-1,3(2H)-dione	5394-18-3	C₁₂H₁₂BrNO₂	详情	详情
(V)	28563	2-[4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butyl]-1H-isoindole-1,3(2H)-dione		C₂₂H₂₃Cl₂N₃O₂	详情	详情
(VI)	28564	4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butylamine		C₁₄H₂₁Cl₂N₃	详情	详情
(VII)	28565	2-biphenylenecarboxylic acid		C₁₃H₈O₂	详情	详情

Extended Information