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【结 构 式】

【分子编号】37174

【品名】3-(dimethylamino)propyl 3-cyano-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxylate

【CA登记号】

【 分 子 式 】C21H23N3O2

【 分 子 量 】349.43264

【元素组成】C 72.18% H 6.63% N 12.03% O 9.16%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(XII)

1) The acetylation of iminodibenzyl (I) with acetyl chloride (A) in refluxing toluene gives N-acetyl-iminodibenzyl (II), which by a Friedel-Kraft's reaction with methyl oxalyl chloride (B) and AlCl3 in CH2Cl2 or CS2 is converted to N-acetyl-3-(methyloxalyl)iminodibenzyl (III). The hydrolysis of (III) with NaOH in methanol-water yields N-acetyl-5-oxalyliminodibenzyl (IV), which by treatment with NaOH in water-ethanol at high temperature affords 3-oxalyliminodibenzyl (V). The reaction of (V) with hydroxylamine and acetic acid gives 3-hydroxylaminooxalyliminodibenzyl (VI), which by heating at 100 C in water is converted into 3-cyanoiminodibenzyl (VII). Finally, this compound is condensed with 3-(dimethylamino)propyl chloride (VIII) by means of NaH in DMF. 2) Compound (VII) can also be condensed with dimethylaminopropyl N,N-dimethylcarbamate (IX) by heating at 250 C. 3) The reaction of (VII) with phosgene gives N-chlorocarbonyl-3-cyanoiminodibenzyl (X), which is condensed with 3-dimethylaminopropanol (XI) to afford 3-cyanoiminodibenzyl-N-carboxylic acid 3-dimethylaminopropyl ester (XII). Finally, this compound is heated at 250 C under reduced pressure.

1 Dostert, P. (Hoffmann-La Roche, Inc.); 3-Cyano-N-(N,N-dimethylaminopropyl)-iminodibenzyl and salts thereof. US 4138482 .
2 Blancafort, P.; Castaner, J.; Owen, R.T.; Serradell, M.N.; RO-11-2465. Drugs Fut 1981, 6, 1, 41.
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) 19273 acetyl chloride 75-36-5 C2H3ClO 详情 详情
(B) 26971 2-methoxy-2-oxoacetyl chloride 5781-53-3 C3H3ClO3 详情 详情
(I) 37165 10,11-dihydro-5H-dibenzo[b,f]azepine 494-19-9 C14H13N 详情 详情
(II) 37166 1-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-1-ethanone C16H15NO 详情 详情
(III) 37167 methyl 2-(5-acetyl-10,11-dihydro-5H-dibenzo[b,f]azepin-3-yl)-2-oxoacetate C19H17NO4 详情 详情
(IV) 37168 2-(5-acetyl-10,11-dihydro-5H-dibenzo[b,f]azepin-3-yl)-2-oxoacetic acid C18H15NO4 详情 详情
(V) 37169 2-(10,11-dihydro-5H-dibenzo[b,f]azepin-3-yl)-2-oxoacetic acid C16H13NO3 详情 详情
(VI) 37170 2-(10,11-dihydro-5H-dibenzo[b,f]azepin-3-yl)-2-(hydroxyimino)acetic acid C16H14N2O3 详情 详情
(VII) 37171 10,11-dihydro-5H-dibenzo[b,f]azepine-3-carbonitrile C15H12N2 详情 详情
(VIII) 24581 3-(Dimethylamino)propyl chloride; 3-Chloro-N,N-dimethyl-1-propanamine 5407-04-5 C5H12ClN 详情 详情
(IX) 37175 3-(dimethylamino)propyl dimethylcarbamate C8H18N2O2 详情 详情
(X) 37172 3-cyano-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carbonyl chloride C16H11ClN2O 详情 详情
(XI) 37173 3-(dimethylamino)-1-propanol 3179-63-3 C5H13NO 详情 详情
(XII) 37174 3-(dimethylamino)propyl 3-cyano-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxylate C21H23N3O2 详情 详情
Extended Information