2-chloro-1-ethoxyethyl ethyl ether; 2-chloro-1,1-diethoxyethane -Drug Synthesis Database

【结构式】

【分子编号】63311

【品名】2-chloro-1-ethoxyethyl ethyl ether; 2-chloro-1,1-diethoxyethane

【CA登记号】

【分子式】C₆H₁₃ClO₂

【分子量】152.62072

【元素组成】C 47.22% H 8.59% Cl 23.23% O 20.97%

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)

Tirapazamine can be obtained by several related ways: 1) By condensation of benzofurazan (I) with cyanamide disodium salt (II) in hot methanol/water. 2) The condensation of 2-nitroaniline (III) with cyanamide (IV) by heating at 100 C gives 3-amino-1,2,4-bezotriazine 1-oxide (V), which is then oxidized with 30% aqueous H2O2 in hot acetic acid. 3) The reaction of 3-hydroxy-1,2,4-benzotriazine 1-oxide (VI) with refluxing POCl3 and dimethylaniline gives 3-chloro-1,2,4-benzotriazine 1-oxide (VII), which by reaction with dry ammonia in ethanol is converted into the corresponding amino derivative (V), already obtained.

参考文献中间体

合成目标

【1】 Schofield, K.; Robbins, R.F.; Polyazabicyclic compounds. Part II. Further derivatives of benzo-1:2:4-triazine. J Chem Soc 1957, 3186.
【2】 Tennant, G.; Mason, J.C.; Heterocyclic N-oxides. Part VI. Synthesis and nuclear magnetic resonance spectra of 3-aminobenzo-1,2,4-triazines and their mono- and di-N-oxides. J Chem Soc B 1970, 911.
【3】 Robinson, C.; Castaner, J.; Tirapazamine. Drugs Fut 1995, 20, 3, 256.
【4】 Ley, K.; Seng, F.; Metzer, K.G. (Bayer AG); 3-Amino-1,2,4-benzotriazine-1,4-di-N-oxides and processes for their preparation. US 3868371; US 3980779; US 4001410 .

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)	11607	2,1,3-benzoxadiazole 1-oxide; 2,1,3-benzoxadiazol-1-ium-1-olate	480-96-6	C₆H₄N₂O₂	详情	详情
(II)	63311	2-chloro-1-ethoxyethyl ethyl ether; 2-chloro-1,1-diethoxyethane		C₆H₁₃ClO₂	详情	详情
(III)	11608	o-Nitroaniline; 2-Nitroaniline; 2-Nitrophenylamine	88-74-4	C₆H₆N₂O₂	详情	详情
(IV)	19648	Cyanamide	420-04-2	CH₂N₂	详情	详情
(V)	11609	3-amino-1,2,4-benzotriazin-1-ium-1-olate; 3-Amino-1,2,4-benzotriazine-1-oxide	5424-06-6	C₇H₆N₄O	详情	详情
(VI)	11610	3-hydroxy-1,2,4-benzotriazin-1-ium-1-olate		C₇H₅N₃O₂	详情	详情
(VII)	11611	3-chloro-1,2,4-benzotriazin-1-ium-1-olate		C₇H₄ClN₃O	详情	详情

合成路线2

该中间体在本合成路线中的序号：

Condensation of benzoil isothiocyanate (I) with 6-amino-m-cresol in refluxing acetone gives N-benzoyl-N'-(2-hydroxy-4-methylphenyl)thiourea (II), which is hydrolyzed with sodium hydroxide to afford N-(2-hydroxy-4-methyl(phenyl)thiourea (III). Thiazolyl ring closure is obtained by addition of chloroacetaldehyde diethylacetal in refluxing ethanol catalyzed by p-toluenesulfonic acid. 2-(2-Hydroxy-4-methylphenyl)aminothiazole is then converted to its hydrochloride sait by bubbling gaseous hydrochloric acid.

参考文献中间体

合成目标

【1】 Alazet, A.; Bonne, C.; Coquelet, C.; Sincholle, D. (Chauvin Laboratories SA); N-Substd. 2-amino-thiazoles, process for their pre. EP 0202157; ES 8900045; FR 2581063; JP 1987077375; US 4785008 .
【2】 Coquelet, C.; Bonne, C.; CBS-113 A. Drugs Fut 1987, 12, 6, 525.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	63311	2-chloro-1-ethoxyethyl ethyl ether; 2-chloro-1,1-diethoxyethane		C₆H₁₃ClO₂	详情	详情
(A)	23533	2-amino-5-methylphenol	2835-98-5	C₇H₉NO	详情	详情
(I)	23530	benzoyl isothiocyanate	532-55-8	C₈H₅NOS	详情	详情
(II)	23531	N-benzoyl-N'-(2-hydroxy-4-methylphenyl)thiourea		C₁₅H₁₄N₂O₂S	详情	详情
(III)	23532	N-(2-hydroxy-4-methylphenyl)thiourea		C₈H₁₀N₂OS	详情	详情

Extended Information