cyclohexanecarbohydrazide -Drug Synthesis Database

【结构式】

【分子编号】61061

【品名】cyclohexanecarbohydrazide

【CA登记号】

【分子式】C₇H₁₄N₂O

【分子量】142.20104

【元素组成】C 59.13% H 9.92% N 19.7% O 11.25%

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：(A)

The reduction of 2-chloroacetylamino-3-(o-chlorobenzoyl)thiophene (I) with NaBH4 in DMF gives 2-chloroacetylamino-3-[(o-chlorophenyl)hydroxymethyl]thiophene (II), which is cyclized by means of sodium isopropoxide in refluxing isopropanol to afford 5-(o-chlorophenyl)thieno[2,3-e]-4,1-oxazepin-2-one (III). The bromination of (III) with Br2 in CHCl3 - pyridine yields 7-bromo-5-(o-chlorophenyl)thieno[2,3-e]-4,1-oxazepin-2-one (IV), which by reaction with P2S5 and NaHCO3 in hot diglyme is converted into 7-bromo-5-(o-chlorophenyl)thieno[2,3-e]-4,1-oxazepin-2-thione (V) (1). The cyclization of (V) with cyclohexanecarboxyl hydrazide (A) in THF gives 7-bromo-5-(o-chlorophenyl)-1-cyclohexylthieno[2,3-e]triazolo[3,4-c]-4,1-oxazepin-2-one (VI). The ring opening of (VI) by treatment with concentrated HBr yields 3-cyclohexyl-4-[3-(o-chlorophenylbromomethyl)-5-bromo-2-thienyl]-5-hydroxymethyl-1,2,4-triazole (VII), which by reaction with SOCl2 is converted into 3-cyclohexyl-4-[3-(o-chlorophenyl-bromomethyl)-5-bromo-2-thienyl]-5-chloromethyl-1,2,4-triazole (VIII). The cyclization of (VIII) with NH3 in methanol a 100 C in a pressure vessel yields 8-bromo-6-(o-chlorophenyl)-1-cyclohexyl-4H-s-triazolo[3,4-c]thieno[2,3-e]-5,6-dihydro-1,4-diazepine (IX), which is finally dehydrogenated by treatment with KMnO4 in refluxing acetone

参考文献中间体

合成目标

【1】 Weber, K.H.; et al. (C.H. Boehringer Sohn); BE 844170; CA 1077475; DD 126744; DE 2531677; DE 2531678; DE 2531679; DE 2533924; FR 2318165; GB 1550679; GB 1550680; JP 7712189; JP 7712193; JP 7714800; JP 7717496; NL 7607871; NL 7607872; US 4201712; ZA 7604212 .
【2】 Blancafort, P.; Serradell, M.N.; Castaner, J.; Owen, R.T.; Ciclotizolam. Drugs Fut 1981, 6, 6, 342.
【3】 Imvamune IND receives approval. Justus Liebigs Ann Chem. 1978, 1257.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(A)	61061	cyclohexanecarbohydrazide	C₇H₁₄N₂O	详情	详情
(I)	61056	2-chloro-N-[3-(2-chlorobenzoyl)-2-thienyl]acetamide	C₁₃H₉Cl₂NO₂S	详情	详情
(II)	61057	2-chloro-N-{3-[(2-chlorophenyl)(hydroxy)methyl]-2-thienyl}acetamide	C₁₃H₁₁Cl₂NO₂S	详情	详情
(III)	61058	5-(2-chlorophenyl)-1,5-dihydrothieno[2,3-e][1,4]oxazepin-2(3H)-one	C₁₃H₁₀ClNO₂S	详情	详情
(IV)	61059	7-bromo-5-(2-chlorophenyl)-1,5-dihydrothieno[2,3-e][1,4]oxazepin-2(3H)-one	C₁₃H₉BrClNO₂S	详情	详情
(V)	60160	(3S,8R,9S,10R,13S,14S,16S,17S)-3-{[tert-butyl(dimethyl)silyl]oxy}-17-[(1S)-1-(2-isopentyl-1,3-dioxolan-2-yl)ethyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-16,17-diol	C₃₅H₆₂O₅Si	详情	详情
(VI)	61062	2-bromo-4-(2-chlorophenyl)-9-cyclohexyl-4H,6H-thieno[2,3-e][1,2,4]triazolo[3,4-c][1,4]oxazepine	C₂₀H₁₉BrClN₃OS	详情	详情
(VII)	60163	4-fluorobenzaldehyde	C₇H₅FO	详情	详情
(VIII)	61064	4-{5-bromo-3-[bromo(2-chlorophenyl)methyl]-2-thienyl}-3-(chloromethyl)-5-cyclohexyl-4H-1,2,4-triazole	C₂₀H₁₉Br₂Cl₂N₃S	详情	详情
(IX)	61065	2-bromo-4-(2-chlorophenyl)-9-cyclohexyl-5,6-dihydro-4H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine	C₂₀H₂₀BrClN₄S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(A)

The reaction of 7-bromo-5-(o-chlorophenyl)-3H-[2,3-e]thieno-1,4-diazepine-2-thione (X) with cyclohexanecarboxyl hydrazide (A) in refluxing dioxane gives 7-bromo-5-(o-chlorophenyl)-2-(cyclohexylcarbonylhydrazino)-3H-[2,3-e]thieno-1,4-diazepine (XI), which is cyclized by treatment with SiO2 in refluxing toluene

参考文献中间体

合成目标

【1】 Werbel, K.H.; et al. (C.H. Boehringer Sohn); .
【2】 Blancafort, P.; Serradell, M.N.; Castaner, J.; Owen, R.T.; Ciclotizolam. Drugs Fut 1981, 6, 6, 342.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(A)	61061	cyclohexanecarbohydrazide	C₇H₁₄N₂O	详情	详情
(X)	61066	7-bromo-5-(2-chlorophenyl)-1,3-dihydro-2H-thieno[2,3-e][1,4]diazepine-2-thione	C₁₃H₈BrClN₂S₂	详情	详情
(XI)	61067	N'-[7-bromo-5-(2-chlorophenyl)-1,3-dihydro-2H-thieno[2,3-e][1,4]diazepin-2-ylidene]cyclohexanecarbohydrazide	C₂₀H₂₀BrClN₄OS	详情	详情

Extended Information