【结 构 式】 |
【药物名称】 【化学名称】N2-[4-(4-Bromophenoxy)phenylsulfonyl]-N1-hydroxy-D-tert-leucinamide 【CA登记号】 【 分 子 式 】C18H21BrN2O5S 【 分 子 量 】457.34647 |
【开发单位】Agouron (Originator) 【药理作用】Antiarthritic Drugs, Oncolytic Drugs, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, Matrix Metalloproteinase Inhibitors |
合成路线1
Chlorosulfonation of 4-bromodiphenyl ether (I) in cold CH2Cl2 afforded the corresponding sulfonyl chloride (II). After silylation of D-tert-leucine (III) with chlorotrimethylsilane and N-methylmopholine, coupling with acid chloride (II) provided sulfonamide (IV). Conversion of (IV) to acid chloride (V) was then achieved by treatment with oxalyl chloride and a catalytic amount of DMF at low temperature. Finally, condensation of (V) with hydroxylamine in aqueous THF gave rise to the target hydroxamic acid.
【1】 Abreo, M.A.; Bender, S.L. (Agouron Pharmaceuticals, Inc.); Metalloproteinase inhibitors, pharmaceutical compsns. containing them and their pharmaceutical uses. EP 0973748; WO 9843963 . |
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) | 35580 | 1-bromo-4-phenoxybenzene; 4-bromophenyl phenyl ether | 101-55-3 | C12H9BrO | 详情 | 详情 |
(II) | 35579 | 4-(4-bromophenoxy)benzenesulfonyl chloride | C12H8BrClO3S | 详情 | 详情 | |
(III) | 35583 | (2R)-2-amino-3,3-dimethylbutyric acid; D-tert-Leucine | 26782-71-8 | C6H13NO2 | 详情 | 详情 |
(IV) | 35581 | (2R)-2-([[4-(4-bromophenoxy)phenyl]sulfonyl]amino)-3,3-dimethylbutyric acid | C18H20BrNO5S | 详情 | 详情 | |
(V) | 35582 | (2R)-2-([[4-(4-bromophenoxy)phenyl]sulfonyl]amino)-3,3-dimethylbutanoyl chloride | C18H19BrClNO4S | 详情 | 详情 |