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【结 构 式】 
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【药物名称】WAY-139799 【化学名称】3-Chloro-4-[2-(1,1-dimethylpropylamino)-3,4-dioxo-1-cyclobutenylaminomethyl]benzonitrile 【CA登记号】202521-43-5 【 分 子 式 】C17H18ClN3O2 【 分 子 量 】331.80491 |
【开发单位】Wyeth Pharmaceuticals (Originator) 【药理作用】RENAL-UROLOGIC DRUGS, Urinary Incontinence Therapy, K(ATP) Channel Activators |
合成路线1
Benzylic bromination of 3-chloro-4-methylbenzonitrile (I) by means of N-bromosuccinimide and azobis(isobutyronitrile) provided bromide (II). Subsequent displacement of the bromine atom of (II) by potassium phthalimide (III) afforded the N-substituted phthalimide (IV), which was then deprotected with ethanolic hydrazine to furnish the primary amine (V).
| 【1】 Antane, M.M.; Herbst, D.R.; McFarlane, G.R.; Gundersen, E.G.; Hirth, B.H.; Quagliato, D.A.; Graceffa, R.F.; Butera, J.A.; Gilbert, A.M. (American Home Products Corp.); Substd. N-arylmethylamino derivs. of cyclobutene-3, 4-diones. US 5763474; US 5780505; WO 9802413 . |
| 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) | 32959 | 3-chloro-4-methylbenzonitrile | C8H6ClN | 详情 | 详情 | |
| (II) | 32960 | 4-(bromomethyl)-3-chlorobenzonitrile | C8H5BrClN | 详情 | 详情 | |
| (III) | 27980 | Diisopropyl (diisopropoxyphosphoryl)methylphosphonate; Tetraisopropyl methylenediphosphonate | 1660-95-3 | C13H30O6P2 | 详情 | 详情 |
| (IV) | 32961 | 3-chloro-4-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]benzonitrile | C16H9ClN2O2 | 详情 | 详情 | |
| (V) | 32962 | 4-(aminomethyl)-3-chlorobenzonitrile | C8H7ClN2 | 详情 | 详情 |
合成路线2
Treatment of 3,4-dibutoxy-3-cyclobutene-1,2-dione (VI) with 1,1-dimethylpropylamine (VII) yielded the amino cyclobutenedione (VIII). Subsequent condensation of (VIII) with 3-chloro-4-(aminomethyl)benzonitrile (V) in THF provided the target diamino derivative.
| 【1】 Antane, M.M.; Herbst, D.R.; McFarlane, G.R.; Gundersen, E.G.; Hirth, B.H.; Quagliato, D.A.; Graceffa, R.F.; Butera, J.A.; Gilbert, A.M. (American Home Products Corp.); Substd. N-arylmethylamino derivs. of cyclobutene-3, 4-diones. US 5763474; US 5780505; WO 9802413 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (V) | 32962 | 4-(aminomethyl)-3-chlorobenzonitrile | C8H7ClN2 | 详情 | 详情 | |
| (VI) | 32963 | 3,4-dibutoxy-3-cyclobutene-1,2-dione | 2892-62-8 | C12H18O4 | 详情 | 详情 |
| (VII) | 24439 | 2-methyl-2-butanamine | 594-39-8 | C5H13N | 详情 | 详情 |
| (VIII) | 32965 | 3-butoxy-4-(tert-pentylamino)-3-cyclobutene-1,2-dione | C13H21NO3 | 详情 | 详情 |