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【结 构 式】 
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【分子编号】32804 【品名】2,4-dichloro-6-methylbenzylamine; (2,4-dichloro-6-methylphenyl)methanamine 【CA登记号】175278-27-0 |
【 分 子 式 】C8H9Cl2N 【 分 子 量 】190.0716 【元素组成】C 50.55% H 4.77% Cl 37.3% N 7.37% |
合成路线1
该中间体在本合成路线中的序号：(IV)A general synthetic route to a series of novel N-aryl and N-benzyl diaminocyclobutenedione derivatives and pertinent SAR data have been reported elsewhere. KCO-616 can be conveniently synthesized in two steps as shown in Scheme 26121401a. An ethanolic solution of 3,4-diethoxy-3-cyclobutene-1,2-dione (I) is allowed to react with tert-amylamine (II) at room temperature for a period of 24 h to give intermediate 3-(1,1-dimethylpropylamino)-4-ethoxy-3-cyclobutene-1,2-dione (III) in 90% isolated, purified yield. The condensation of this compound with 2,4-dichloro-6-methylbenzylamine (IV, recrystallized from boiling diethyl ether) in ethanol at room temperature for 24 h affords analytically pure 3-(2,4-dichloro-6-methylbenzylamino)-4-(1,1-dimethylpropylamino)-3-cyclobutene-1,2-dione (KCO-616) in 92% yield.
| 【1】 Butera, J.A.; et al.; Substituted N-aryl-1,2-diaminocyclobutene-3,4-diones. I. N-Cyanoguanidine bioisosteres possessing in vivo bladder selectivity. 214th ACS Natl Meet (Sept. 7-11, Las Vegas) 1997, Abst MEDI 044. |
| 【2】 McFarlane, G.R.; Gundersen, E.G.; Elokdah, H.; et al.; Benzylamino analogs of 1,2-diaminocyclobutene-3,4-dione as novel KATP-channel openers targeted for treatment of urge urinary incontinence . 218th ACS Natl Meet (Aug 22 1999, New Orleans) 1999, Abst MEDI 35. |
| 【3】 Antane, M.M.; Butera, J.A.; Antane, S.A.; et al.; Design and SAR of novel potassium channel openers targeted for urge urinary incontinence. I. N-Cyanoguanidine bioisosteres possessing in vivo bladder selectivity. J Med Chem 2000, 43, 6, 1187-1202. |
| 【4】 Butera, J.A.; Argentieri, T.M.; KCO-616. Drugs Fut 2000, 25, 3, 239. |
| 【5】 Antane, M.M.; Argentieri, T.M.; Gilbert, A.M.; et al.; Desing and SAR of novel potassium channel openers targeted for urge urinary incontinence. 2. Selective and potent benzylamino cyclobutenediones. J Med Chem 2000, 43, 6, 1203. |
| 【6】 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) | 30975 | 3,4-diethoxy-3-cyclobutene-1,2-dione | 5231-87-8 | C8H10O4 | 详情 | 详情 |
| (II) | 24439 | 2-methyl-2-butanamine | 594-39-8 | C5H13N | 详情 | 详情 |
| (III) | 32803 | 3-ethoxy-4-(tert-pentylamino)-3-cyclobutene-1,2-dione | C11H17NO3 | 详情 | 详情 | |
| (IV) | 32804 | 2,4-dichloro-6-methylbenzylamine; (2,4-dichloro-6-methylphenyl)methanamine | 175278-27-0 | C8H9Cl2N | 详情 | 详情 |