|
【结 构 式】 
|
【分子编号】60909 【品名】4'-(bromomethyl)-N-(3,4-dimethyl-5-isoxazolyl)-2'-(1,3-dioxolan-2-yl)-N-[(2-methoxyethoxy)methyl][1,1'-biphenyl]-2-sulfonamide 【CA登记号】 |
【 分 子 式 】C25H29BrN2O7S 【 分 子 量 】581.48454 【元素组成】C 51.64% H 5.03% Br 13.74% N 4.82% O 19.26% S 5.51% |
合成路线1
该中间体在本合成路线中的序号：(VIII)The intermediate biphenyl aldehyde (XI) is prepared by two related methods. 4-Bromo-3-methylbenzonitrile (I) is oxidized to aldehyde (II) via radical bromination with N-bromosuccinimide/benzoyl peroxide, followed by treatment with trimethylamine N-oxide. Suzuki coupling of aryl bromide (II) with the pinacol boronate (III) affords biphenyl (IV). After protection of the aldehyde moiety of (IV) as the corresponding ethylene ketal (V), its cyano group is reduced to aldehyde (VI) employing DIBAL in THF. Subsequent reduction of (VI) with NaBH4 leads to alcohol (VII), which is further converted into the benzyl bromide (VIII) by means of CBr4/PPh3. Bromide (VIII) is condensed with the spiro imidazolone (IX) in the presence of NaH, to produce (X). Then acidic hydrolysis of the ethylene ketal and SEM groups of (X) gives rise to the intermediate aldehyde (XI)
| 【1】 Macor, J.E.; Murugesan, N.; Gu, Z.; Tellew, J.E. (Bristol-Myers Squibb Co.); Biphenyl sulfonamides as dual angiotensin endothelin receptor antagonists. EP 1094816; JP 2002519380; US 2002143024; WO 0001389 . |
| 【2】 Macor, J.E.; Murugesan, N.; Gu, Z.; Tellew, J.E. (Bristol-Myers Squibb Co.); Biphenyl sulfonamides as dual angiotensin endothelin receptor antagonists. EP 1237888; WO 0144239 . |
| 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) | 60902 | 4-bromo-3-methylbenzonitrile | C8H6BrN | 详情 | 详情 | |
| (II) | 60903 | 4-bromo-3-formylbenzonitrile | C8H4BrNO | 详情 | 详情 | |
| (III) | 60904 | N-(3,4-dimethyl-5-isoxazolyl)-N-[(2-methoxyethoxy)methyl]-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenesulfonamide | C21H31BN2O7S | 详情 | 详情 | |
| (IV) | 60905 | 4'-cyano-N-(3,4-dimethyl-5-isoxazolyl)-2'-formyl-N-[(2-methoxyethoxy)methyl][1,1'-biphenyl]-2-sulfonamide | C23H23N3O6S | 详情 | 详情 | |
| (V) | 60906 | 4'-cyano-N-(3,4-dimethyl-5-isoxazolyl)-2'-(1,3-dioxolan-2-yl)-N-[(2-methoxyethoxy)methyl][1,1'-biphenyl]-2-sulfonamide | C25H27N3O7S | 详情 | 详情 | |
| (VI) | 60907 | N-(3,4-dimethyl-5-isoxazolyl)-2'-(1,3-dioxolan-2-yl)-4'-formyl-N-[(2-methoxyethoxy)methyl][1,1'-biphenyl]-2-sulfonamide | C25H28N2O8S | 详情 | 详情 | |
| (VII) | 60908 | N-(3,4-dimethyl-5-isoxazolyl)-2'-(1,3-dioxolan-2-yl)-4'-(hydroxymethyl)-N-[(2-methoxyethoxy)methyl][1,1'-biphenyl]-2-sulfonamide | C25H30N2O8S | 详情 | 详情 | |
| (VIII) | 60909 | 4'-(bromomethyl)-N-(3,4-dimethyl-5-isoxazolyl)-2'-(1,3-dioxolan-2-yl)-N-[(2-methoxyethoxy)methyl][1,1'-biphenyl]-2-sulfonamide | C25H29BrN2O7S | 详情 | 详情 | |
| (IX) | 15118 | 2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one; 1,3-Diazaspirol[4,4]non-1-en-4-one,2-butyl | 151257-01-1 | C11H18N2O | 详情 | 详情 |
| (X) | 60910 | 4'-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2'-(1,3-dioxolan-2-yl)-N-[(2-methoxyethoxy)methyl][1,1'-biphenyl]-2-sulfonamide | C36H46N4O8S | 详情 | 详情 | |
| (XI) | 60911 | 4'-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2'-formyl[1,1'-biphenyl]-2-sulfonamide | C30H34N4O5S | 详情 | 详情 |