3-methoxybenzonitrile -Drug Synthesis Database

【结构式】

【分子编号】36250

【品名】3-methoxybenzonitrile

【CA登记号】1527-89-5

【分子式】C₈H₇NO

【分子量】133.14972

【元素组成】C 72.17% H 5.3% N 10.52% O 12.02%

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：(I)

A new method for the synthesis of DL-111-IT has been reported: By cyclization of m-methoxybenzonitrile (I) with ethoxybenzoylhydrazide (II) in refluxing methanol.

参考文献中间体

合成目标

【1】 Neelima; Bhaduri, A.P.; Reaction of substituted acid hydrazides with substituted benzonitriles: Formatio of isomeric triazoles. Indian J Chem 1983, 22B, 1, 79-80.

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)	36250	3-methoxybenzonitrile	1527-89-5	C₈H₇NO	详情	详情
(II)	34364	2-ethylbenzohydrazide		C₉H₁₂N₂O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IX)

ZK-807834 is obtained by condensation of the diaryl ether (I) with the phenol (II) by means of K2CO3 to afford the bisaryl ether (III). Reaction of the cyano group of (III), first with HCl in ethanol and then with ammonia, yields the corresponding amidino compound (IV), which is finally demethylated with HBr.

参考文献中间体

合成目标

【2】 Discovery of N-[2-[5-[amino(imino)methyl]-2-hydroxyphenoxy]-3,5-difluoro-6-[3-(4,5-dihydro-1-methyl-1H-imidazol-2-yl)phenoxy]pyridin-4-yl]-N-methylglycine (ZK-807834): A potent, selective, and orally active inhibitor of the blood coagulation enzyme factor. J Med Chem 1998, 41, 19, 3557.
【1】 Ricart-Diaz, M.; Castaner, J.; ZK-807834. Drugs Fut 2002, 27, 8, 748.
【3】 Buckman, B.O.; Davey, D.D.; Guilford, W.J.; Morrissey, M.M.; Ng, H.P.; Phillips, G.B.; Wu, S.C.; Xu, W. (Berlex Laboratories, Inc.); Benzamidine derivs. their preparation and their use as anti-coagulants. EP 0813525; US 5691364; WO 9628427 .

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)	54575	2-[[2-(5-cyano-2-methoxyphenoxy)-3,5,6-trifluoro-4-pyridinyl](methyl)amino]acetamide		C₁₆H₁₃F₃N₄O₃	详情	详情
(II)	54576	2-(3-methoxyphenyl)-1-methyl-4,5-dihydro-1H-imidazole; methyl 3-(1-methyl-4,5-dihydro-1H-imidazol-2-yl)phenyl ether		C₁₁H₁₄N₂O	详情	详情
(III)	54578	2-[{2-(5-cyano-2-methoxyphenoxy)-3,5-difluoro-6-[3-(1-methyl-4,5-dihydro-1H-imidazol-2-yl)phenoxy]-4-pyridinyl}(methyl)amino]acetamide		C₂₆H₂₄F₂N₆O₄	详情	详情
(IV)	54579	2-[{2-{5-[amino(imino)methyl]-2-methoxyphenoxy}-3,5-difluoro-6-[3-(1-methyl-4,5-dihydro-1H-imidazol-2-yl)phenoxy]-4-pyridinyl}(methyl)amino]acetamide		C₂₆H₂₇F₂N₇O₄	详情	详情
(V)	54571	Pentafluoropyridine; Perfluoropyridine	700-16-3	C₅F₅N	详情	详情
(VI)	54572	2-(methylamino)acetamide		C₃H₈N₂O	详情	详情
(VII)	54573	2-[methyl(2,3,5,6-tetrafluoro-4-pyridinyl)amino]acetamide		C₈H₇F₄N₃O	详情	详情
(VIII)	54574	3-hydroxy-4-methoxybenzonitrile	52805-46-6	C₈H₇NO₂	详情	详情
(IX)	36250	3-methoxybenzonitrile	1527-89-5	C₈H₇NO	详情	详情
(X)	27777	N-(2-aminoethyl)-N-methylamine	109-81-9	C₃H₁₀N₂	详情	详情
(XI)	54575	2-[[2-(5-cyano-2-methoxyphenoxy)-3,5,6-trifluoro-4-pyridinyl](methyl)amino]acetamide		C₁₆H₁₃F₃N₄O₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

3-Methoxybenzonitrile (I) was converted to the corresponding imidate (II) by treatment with ethanolic HCl. Condensation of (II) with aminoacetaldehyde diethyl acetal (III) gave amidine (IV), which was cyclized with diethyl ethoxymethylenemalonate (V) in refluxing ethanol to yield the pyrimidinone (VI). Hydrolysis of the ethyl ester function of (VI) by treatment with LiI in hot pyridine provided acid (VII). This was subjected to a Curtius rearrangement with diphenylphosphoryl azide, and the intermediate isocyanate was condensed with benzyl alcohol to produce the benzyl carbamate (VIII). Acid hydrolysis of the diethyl acetal group of (VIII), followed by oxidation of the resulting aldehyde with sodium chlorite, furnished the carboxylic acid (IX).

参考文献中间体

合成目标

【1】 Akahoshi, F.; Ashimori, A.; Yoshimura, T.; Eda, M.; Sakashita, H.; Nakajima, M.; Imada, T. (Welfide Corporation); Novel heterocyclic amide cpds. and medicinal uses thereof. EP 0940400; US 6080738; WO 9818794 .

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)	36250	3-methoxybenzonitrile	1527-89-5	C₈H₇NO	详情	详情
(II)	34363	ethyl 3-methoxybenzenecarboximidoate		C₁₀H₁₃NO₂	详情	详情
(III)	10331	2,2-Diethoxy-1-ethanamine; 2,2-Diethoxyethylamine; Aminoacetaldehyde diethyl acetal	645-36-3	C₆H₁₅NO₂	详情	详情
(IV)	48623	N-(2,2-diethoxyethyl)-3-methoxybenzenecarboximidamide		C₁₄H₂₂N₂O₃	详情	详情
(V)	14088	Diethyl ethoxymethylenemalonate; Diethyl 2-(ethoxymethylene)malonate	87-13-8	C₁₀H₁₆O₅	详情	详情
(VI)	48624	ethyl 1-(2,2-diethoxyethyl)-2-(3-methoxyphenyl)-6-oxo-1,6-dihydro-5-pyrimidinecarboxylate		C₂₀H₂₆N₂O₆	详情	详情
(VII)	48625	1-(2,2-diethoxyethyl)-2-(3-methoxyphenyl)-6-oxo-1,6-dihydro-5-pyrimidinecarboxylic acid		C₁₈H₂₂N₂O₆	详情	详情
(VIII)	48626	benzyl 1-(2,2-diethoxyethyl)-2-(3-methoxyphenyl)-6-oxo-1,6-dihydro-5-pyrimidinylcarbamate		C₂₅H₂₉N₃O₆	详情	详情
(IX)	48627	2-[5-[[(benzyloxy)carbonyl]amino]-2-(3-methoxyphenyl)-6-oxo-1(6H)-pyrimidinyl]acetic acid		C₂₁H₁₉N₃O₆	详情	详情

Extended Information