Diethoxymethyl acetate -Drug Synthesis Database

【结构式】

【分子编号】17661

【品名】Diethoxymethyl acetate

【CA登记号】14036-06-7

【分子式】C₇H₁₄O₄

【分子量】162.18576

【元素组成】C 51.84% H 8.7% O 39.46%

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：(VI)

The synthesis of [14C]-labeled piritrexim has been described: The condensation of 2,5-dimethoxybenzaldehyde (I) with acetone in aqueous NaOH gives 4-(2,5-dimethoxyphenyl)-3-(E)-buten-2-one (II), which is hydrogenated with H2 over Pd/C in methanol to give 4-(2,5-dimethoxyphenyl)-2-butanone (III). The condensation of (III) with malononitrile (IV) by means of acetic acid-sodium acetate in refluxing toluene yields 2-cyano-5-(2,5-dimethoxyphenyl)-3-methyl-2-pentenenitrile (V), which is condensed with acetic acid diethoxymethyl ester (VI) at 105 C to afford the corresponding diethoxymethyl derivative (VII). The cyclization of (VII) with 32% HBr in acetic acid affords 2-bromo-5-(2,5-dimethoxybenzyl)-4-methylpyridine-3-carbonitrile (VIII), which is finally cyclized again with [14C]-labeled guanidine (IX) by means of NaH in refluxing tert-butyl alcohol.

参考文献中间体

合成目标

【1】 Wisowaty, J.C.; Darnofall, M.E.; Hill, J.A.; Synthesis of carbon-14 labelled piritrexim - A potential anticancer agent. J Label Compd Radiopharm 1993, 33, 12, 1119.

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)	10174	2,5-Dimethoxybenzaldehyde	93-02-7	C₉H₁₀O₃	详情	详情
(II)	10175	(E)-4-(2,5-Dimethoxyphenyl)-3-buten-2-one		C₁₂H₁₄O₃	详情	详情
(III)	10176	4-(2,5-Dimethoxyphenyl)-2-butanone		C₁₂H₁₆O₃	详情	详情
(IV)	12061	Malononitrile	109-77-3	C₃H₂N₂	详情	详情
(V)	10177	2-[3-(2,5-Dimethoxyphenyl)-1-methylpropylidene]malononitrile		C₁₅H₁₆N₂O₂	详情	详情
(VI)	17661	Diethoxymethyl acetate	14036-06-7	C₇H₁₄O₄	详情	详情
(VII)	10178	2-[2-(2,5-Dimethoxybenzyl)-3,3-diethoxy-1-methylpropylidene]malononitrile		C₂₀H₂₆N₂O₄	详情	详情
(VIII)	10179	2-Bromo-5-(2,5-dimethoxybenzyl)-4-methylnicotinonitrile		C₁₆H₁₅BrN₂O₂	详情	详情
(IX)	14790	Guanidine	113-00-8	CH₅N₃	详情	详情
(IX)	44601	guanidine		CH₅N₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XX)

3) The condensation of (±)-cis-4-acetamido-2-cyclopentenylmethyl acetate (XIV) with 2-amino-4,6-dichloropyrimidine (XV) by means of Ba(OH)2 and triethylamine in refluxing butanol gives the expected condensation product (XVI), which is treated with 4-chlorophenyldiazonium chloride (XVII) in water/acetic acid to yield the corresponding azo-compound (XVIII). The reduction of (XVIII) with Zn/acetic acid in ethanol affords the diamine (XIX), which is cyclized with refluxing diethoxymethyl acetate (XX) to afford the corresponding purine (XXI). The reaction of (XXI) with cyclopropylamine (X) in refluxing ethanol affords racemic abacavir (XXII), which is phosphorylated with POCl3 giving the racemic 4'-O-phosphate (XXIII). Finally, this compound is submitted to stereoselective enzymatic dephosphorylation using snake venom 5'-nucleotidase (EC 3.1.3.5) from Crotalus atrox yielding the (-)-enantiomer, abacavir.

参考文献中间体

合成目标

【1】 Graul, A.; Castaner, J.; Leeson, P.A.; Abacavir Sulfate. Drugs Fut 1998, 23, 11, 1155-1167.
【2】 Daluge, S.M. (Glaxo Wellcome plc); Therapeutic nucleosides. EP 0434450; JP 1996092252; JP 1999158160; JP 1999343292 .
【3】 Daluge, S.M. (Glaxo Wellcome plc); Therapeutic nucleosides. AU 8937025; EP 0349242; JP 1990045486; JP 1999139976; US 5034394; US 5089500 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(X)	12263	Cyclopropylamine; Cyclopropanamine	765-30-0	C₃H₇N	详情	详情
(XIV)	17655	(1S,4R)-4-(acetamido)-2-cyclopenten-1-yl acetate		C₉H₁₃NO₃	详情	详情
(XV)	14404	4,6-dichloro-2-pyrimidinamine; 2-Amino-4,6-dichloropyrimidine; 4,6-dichloro-2-pyrimidinylamine	56-05-3	C₄H₃Cl₂N₃	详情	详情
(XVI)	17657	[(1S,4R)-4-[(2-amino-6-chloro-4-pyrimidinyl)amino]-2-cyclopenten-1-yl]methanol		C₁₀H₁₃ClN₄O	详情	详情
(XVII)	10197	4-Chlorobenzenediazonium chloride		C₆H₄Cl₂N₂	详情	详情
(XVIII)	17659	[(1S,4R)-4-([2-amino-6-chloro-5-[(E)-2-(4-chlorophenyl)diazenyl]-4-pyrimidinyl]amino)-2-cyclopenten-1-yl]methanol		C₁₆H₁₆Cl₂N₆O	详情	详情
(XIX)	17660	[(1S,4R)-4-[(2,5-diamino-6-chloro-4-pyrimidinyl)amino]-2-cyclopenten-1-yl]methanol		C₁₀H₁₄ClN₅O	详情	详情
(XX)	17661	Diethoxymethyl acetate	14036-06-7	C₇H₁₄O₄	详情	详情
(XXI)	17650	[(1S,4R)-4-(2-amino-6-chloro-9H-purin-9-yl)-2-cyclopenten-1-yl]methanol		C₁₁H₁₂ClN₅O	详情	详情
(XXII)	17663	[(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopenten-1-yl]methanol		C₁₄H₁₈N₆O	详情	详情
(XXIII)	17664	[(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopenten-1-yl]methyl dihydrogen phosphate		C₁₄H₁₉N₆O₄P	详情	详情

合成路线3

该中间体在本合成路线中的序号：(V)

The reaction of 4-chlorobenzoylhydrazide (I) with S-methyl isothiourea sulfate in aqueous NaOH gave guanidine (II) which, on heating at 220 C, was converted into aminotriazole (III). Subsequent condensation with methyl isothiocyanate in DMF gave thiocarbonyl triazole (IV). Finally, cyclization with diethoxymethyl acetate at 90 C provided the target triazolotriazine.

参考文献中间体

合成目标

【1】 Akahoshi, F.; et al.; Synthesis and pharmacological activity of triazolo[1,5-a]triazine derivatives inhibiting eosinophilia. J Med Chem 1998, 41, 16, 2985-2993.
【2】 Naito, Y.; et al.; Synthesis and pharmacological activity of triazole derivatives inhibiting eosinophilia. J Med Chem 1996, 39, 15, 3019-3029.
【3】 Akahoshi, F.; Okada, T.; Takeda, S.; Naito, Y.; Fukaya, C.; Kuwahara, S.; Kajii, M.; Nishimura, H.; Sugiura, M. (Welfide Corporation); Triazole derivs. and pharmaceutical use thereof. EP 0710654; JP 1995082270; JP 1995097321; JP 1995101942; US 5750545; WO 9503286 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	10272	[[Amino(imino)methyl]sulfanyl]methane	2986-19-8	C₂H₆N₂S	详情	详情
(I)	18216	4-chlorobenzohydrazide; p-chloro-benzoylhydrazine	536-40-3	C₇H₇ClN₂O	详情	详情
(II)	18217	2-(4-chlorobenzoyl)-1-hydrazinecarboximidamide		C₈H₉ClN₄O	详情	详情
(III)	18218	5-(4-chlorophenyl)-1H-1,2,4-triazol-3-ylamine; 5-(4-chlorophenyl)-1H-1,2,4-triazol-3-amine		C₈H₇ClN₄	详情	详情
(IV)	18219	5-amino-3-(4-chlorophenyl)-N-methyl-1H-1,2,4-triazole-1-carbothioamide		C₁₀H₁₀ClN₅S	详情	详情
(V)	17661	Diethoxymethyl acetate	14036-06-7	C₇H₁₄O₄	详情	详情

Extended Information