【结 构 式】 |
【分子编号】37171 【品名】10,11-dihydro-5H-dibenzo[b,f]azepine-3-carbonitrile 【CA登记号】 |
【 分 子 式 】C15H12N2 【 分 子 量 】220.27376 【元素组成】C 81.79% H 5.49% N 12.72% |
合成路线1
该中间体在本合成路线中的序号:(VII)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 |