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【结 构 式】

【药物名称】XU-057

【化学名称】3-[3-(4-Amidinophenyloxymethyl)benzamido]-2(R)-(butoxycarboxamido)propionic acid methyl ester trifluoroacetate

【CA登记号】

【 分 子 式 】C26H31F3N4O8

【 分 子 量 】584.55417

【开发单位】Bristol-Myers Squibb (Originator)

【药理作用】Antiplatelet Therapy, Coagulation Disorders Therapy, HEMATOLOGIC DRUGS, Integrin alphaIIbbeta3 (Fibrinogen gpIIb/IIIa) Antagonists

合成路线1

The esterification of (S)-3-amino-2-(benzyloxycarbonylamino)propionic acid (I) with methanol/HCl gives the expected methyl ester (II), which is protected with di-tert-butyl dicarbonate and triethylamine in chloroform to the fully protected compound (III). The debenzylation of (III) by treatment with formic acid over Pd/C in methanol yields the 2-amino compound (IV), which is acylated with butyl chloroformate and NaHCO3 in THF affording 2(S)-(n-butoxycarbonylamino)-3-(tert-butoxycarbonylamino)propionic acid methyl ester (V).The selctive deacylation of (V) with trifluoroacetic acid in dichloromethane affords the 3-amino-2(S)-(n-butoxycarbonylamino)propionic ester (VI), which is acylated with 3-(chloromethyl)benzoyl chloride (VII) and triethylamine in dichloromethane giving the benzamido ester (VIII). The condensation of (VIII) with 4-hydroxybenzonitrile (IX) by means of NaH or K2CO3 yields the precursor (X), which is finally treated first with HCl in methanol, and then with NH3 in the same solvent to providde the target compound.

1 Degrado, W.F.; Xue, C.-B. (DuPont Pharmaceuticals Co.); Cpds. containing basic and acidic termini useful as fibrinogen receptor antagonists. US 5563158; WO 9518111 .
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) 18008 (2S)-3-amino-2-[[(benzyloxy)carbonyl]amino]propionic acid; N(alpha)-Z-L-2,3-diaminopropionic acid 35761-26-3 C11H14N2O4 详情 详情
(II) 25093 methyl (2S)-3-amino-2-[[(benzyloxy)carbonyl]amino]propanoate C12H16N2O4 详情 详情
(III) 25094 methyl (2S)-2-[[(benzyloxy)carbonyl]amino]-3-[(tert-butoxycarbonyl)amino]propanoate C17H24N2O6 详情 详情
(IV) 25095 methyl (2S)-2-amino-3-[(tert-butoxycarbonyl)amino]propanoate C9H18N2O4 详情 详情
(V) 25096 methyl (2S)-3-[(tert-butoxycarbonyl)amino]-2-[(butoxycarbonyl)amino]propanoate C14H26N2O6 详情 详情
(VI) 25097 methyl (2S)-3-amino-2-[(butoxycarbonyl)amino]propanoate C9H18N2O4 详情 详情
(VII) 25107 3-(chloromethyl)benzoyl chloride 63024-77-1 C8H6Cl2O 详情 详情
(VIII) 25108 methyl (2S)-2-[(butoxycarbonyl)amino]-3-[[3-(chloromethyl)benzoyl]amino]propanoate C17H23ClN2O5 详情 详情
(IX) 25109 4-hydroxybenzonitrile 767-00-0 C7H5NO 详情 详情
(X) 25110 methyl (2S)-2-[(butoxycarbonyl)amino]-3-([3-[(4-cyanophenoxy)methyl]benzoyl]amino)propanoate C24H27N3O6 详情 详情
Extended Information