【结 构 式】 |
【分子编号】22362 【品名】ethyl 3-[[5-amino-2-(benzhydrylamino)benzoyl]amino]propanoate 【CA登记号】 |
【 分 子 式 】C25H27N3O3 【 分 子 量 】417.5078 【元素组成】C 71.92% H 6.52% N 10.06% O 11.5% |
合成路线1
该中间体在本合成路线中的序号:(XVI)2) An improved procedure consisted of condensation of 5-nitroisatoic anhydride (I) with beta-alanine ethyl ester (V) to give amide (XIV). The amino group of (XIV) was protected with benzhydryl bromide (VII) yielding (XV), and then the nitro group of (XV) was reduced to aniline (XVI) by catalytic transfer hydrogenation. Protection of the amine of (XVI) as the tert-butyl carbamate (XVIII) was effected using 2-(tert-butoxycarbonyloxymino)-2-phenylacetonitrile (XVII). The sequence of condensation of (XVIII) with bromoacetyl bromide (IX), followed by cyclization of the intermediate bromoacetamide with DBU provided the benzodiazepinedione (XIX). Hydrogenolysis of the N-benzhydryl group of (XIX) in the presence of Pearlman's catalyst, followed by treatment with trimethylsilyl azide furnished the tetrazole (XX). The Boc group of (XX) was deprotected with trifluoroacetic acid, and subsequent coupling with 4-cyanobenzoyl chloride (III) gave amide (XXI). The cyano group was of (XXI) then converted to hydroxyamidine (XXII) with hydroxylamine. Catalytic hydrogenation of (XXII) in the presence of Ac2O and AcOH produced the corresponding amidine. Finally, the ester group was hydrolyzed with LiOH.
【1】 Robarge, K.D.; Dina, M.S.; Somers, T.C.; Lee, A.; Rawson, T.E.; Olivero, A.G.; Tischler, M.H.; Webb, R.R. II; Weese, K.J.; Aliagas, I.; Blackburn, B.K.; Preparation and biological activity of novel tricyclic GPIIb/IIIa antagonists. Bioorg Med Chem 1998, 6, 12, 2345. |
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) | 22347 | 5-Nitroisatoic anhydride; 6-nitro-2H-3,1-benzoxazine-2,4(1H)-dione | 4693-02-1 | C8H4N2O5 | 详情 | 详情 |
(III) | 19280 | 4-cyanobenzoyl chloride | 6068-72-0 | C8H4ClNO | 详情 | 详情 |
(VII) | 17639 | beta-Alanine, ethyl ester; ethyl 3-aminopropanoate | 924-73-2 | C5H11NO2 | 详情 | 详情 |
(IX) | 14005 | 2-Bromoacetyl bromide; Bromoacetyl bromide | 598-21-0 | C2H2Br2O | 详情 | 详情 |
(XIV) | 22360 | ethyl 3-[(2-amino-5-nitrobenzoyl)amino]propanoate | C12H15N3O5 | 详情 | 详情 | |
(XV) | 22361 | ethyl 3-[[2-(benzhydrylamino)-5-nitrobenzoyl]amino]propanoate | C25H25N3O5 | 详情 | 详情 | |
(XVI) | 22362 | ethyl 3-[[5-amino-2-(benzhydrylamino)benzoyl]amino]propanoate | C25H27N3O3 | 详情 | 详情 | |
(XVII) | 22363 | 2-[[(tert-butoxycarbonyl)oxy]imino]-2-phenylacetonitrile | 58632-95-4 | C13H14N2O3 | 详情 | 详情 |
(XVIII) | 22364 | ethyl 3-([2-(benzhydrylamino)-5-[(tert-butoxycarbonyl)amino]benzoyl]amino)propanoate | C30H35N3O5 | 详情 | 详情 | |
(XIX) | 22365 | ethyl 3-[1-benzhydryl-7-[(tert-butoxycarbonyl)amino]-2,5-dioxo-1,2,3,5-tetrahydro-4H-1,4-benzodiazepin-4-yl]propanoate | C32H35N3O6 | 详情 | 详情 | |
(XX) | 22366 | ethyl 3-[8-[(tert-butoxycarbonyl)amino]-6-oxo-4H-[1,2,3,4]tetraazolo[1,5-a][1,4]benzodiazepin-5(6H)-yl]propanoate | C19H24N6O5 | 详情 | 详情 | |
(XXI) | 22357 | ethyl 3-[8-[(4-cyanobenzoyl)amino]-6-oxo-4H-[1,2,3,4]tetraazolo[1,5-a][1,4]benzodiazepin-5(6H)-yl]propanoate | C22H19N7O4 | 详情 | 详情 | |
(XXII) | 22368 | ethyl 3-[8-([4-[amino(hydroxyimino)methyl]benzoyl]amino)-6-oxo-4H-[1,2,3,4]tetraazolo[1,5-a][1,4]benzodiazepin-5(6H)-yl]propanoate | C22H22N8O5 | 详情 | 详情 |