【结 构 式】 |
【分子编号】54054 【品名】6-chloro-2,10-diazatetracyclo[11.2.1.0~2,12~.0~4,9~]hexadeca-4,6,8,14-tetraene-3,11-dione 【CA登记号】n/a |
【 分 子 式 】C14H11ClN2O2 【 分 子 量 】274.70632 【元素组成】C 61.21% H 4.04% Cl 12.91% N 10.2% O 11.65% |
合成路线1
该中间体在本合成路线中的序号:(VIII)The cyclization of 2-oxoacetic acid ethyl ester (I), 1-phenylethylamine (II) and cyclopentadiene (III) by means of BF3 and TFA in dichloromethane gives the 2-azabicyclo[2.2.1]heptene (IV), which is debenzylated with H2 over Pd/C in ethanol to yield 2-azabicyclo[2.2.1]hept-5-ene-3-carboxylic acid ethyl ester (V) The acylation of (V) with 5-chloro-2-nitrobenzoyl chloride (VI) and TEA in dichloromethane affords the bicyclic amide (VII), which is submitted to a reductive cyclization with Fe in refluxing acetic acid to afford the polycyclic benzodiazepinedione (VIII). The reduction of the carbonyl groups of (VIII) by means of LiAlH4 in THF provides the benzodiazepine (IX), which is acylated with 4-nitrobenzoyl chloride (X) and TEA in dichloromethane to give the polycyclic amide (XI). The reduction of the nitro group of (XI) with Zn and NH4Cl in refluxing methanol yields the corresponding amino derivative (XII), which is finally acylated with 4'-methylbiphenyl-2-carbonyl chloride (XIII) and TEA in dichloromethane to furnish the target polycyclic benzodiazepine.
【1】 Dyatkin, A.B.; Demarest, K.; Look, R.; Maryanoff, B.E.; Hoekstra, W.J.; Gunnet, J.; Andrade-Gordon, P.; DeGaravilla, L.; Hlasta, D.J.; Structurally novel V2-selective and dual V1A/V2 vasopressin receptor antagonists. 223rd ACS Natl Meet (April 7 2002, Orlando) 2002, Abst MEDI 35. |
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) | 48591 | Ethyl glyoxylate; Ethyl oxoacetate; Glyoxylic acid ethyl ester | 924-44-7 | C4H6O3 | 详情 | 详情 |
(II) | 11183 | 1,3-Cyclopentadiene | C5H6 | 详情 | 详情 | |
(III) | 15148 | 1-phenylethylamine; DL-a-methylbenzylamine; 1-phenyl-1-ethanamine | 618-36-0 | C8H11N | 详情 | 详情 |
(IV) | 54051 | ethyl 2-(1-phenylethyl)-2-azabicyclo[2.2.1]hept-5-ene-3-carboxylate | n/a | C17H21NO2 | 详情 | 详情 |
(V) | 54052 | ethyl 2-azabicyclo[2.2.1]hept-5-ene-3-carboxylate | n/a | C9H13NO2 | 详情 | 详情 |
(VI) | 44133 | 5-chloro-2-nitrobenzoyl chloride | C7H3Cl2NO3 | 详情 | 详情 | |
(VII) | 54053 | ethyl 2-(5-chloro-2-nitrobenzoyl)-2-azabicyclo[2.2.1]hept-5-ene-3-carboxylate | n/a | C16H15ClN2O5 | 详情 | 详情 |
(VIII) | 54054 | 6-chloro-2,10-diazatetracyclo[11.2.1.0~2,12~.0~4,9~]hexadeca-4,6,8,14-tetraene-3,11-dione | n/a | C14H11ClN2O2 | 详情 | 详情 |
(IX) | 54055 | 6-chloro-2,10-diazatetracyclo[11.2.1.0~2,12~.0~4,9~]hexadeca-4,6,8,14-tetraene | n/a | C14H15ClN2 | 详情 | 详情 |
(X) | 18941 | p-nitrobenzoyl chloride; 4-nitrobenzoyl chloride | 122-04-3 | C7H4ClNO3 | 详情 | 详情 |
(XI) | 54056 | (6-chloro-2,10-diazatetracyclo[11.2.1.0~2,12~.0~4,9~]hexadeca-4,6,8,14-tetraen-10-yl)(4-nitrophenyl)methanone | n/a | C21H18ClN3O3 | 详情 | 详情 |
(XII) | 54057 | (4-aminophenyl)(6-chloro-2,10-diazatetracyclo[11.2.1.0~2,12~.0~4,9~]hexadeca-4,6,8,14-tetraen-10-yl)methanone | n/a | C21H20ClN3O | 详情 | 详情 |
(XIII) | 54058 | 4'-methyl[1,1'-biphenyl]-2-carbonyl chloride | n/a | C14H11ClO | 详情 | 详情 |