|
【结 构 式】 
|
【分子编号】62330 【品名】 【CA登记号】 |
【 分 子 式 】C7H18N4 【 分 子 量 】158.24688 【元素组成】C 53.13% H 11.46% N 35.4% |
合成路线1
该中间体在本合成路线中的序号：(IV)Treatment of thiourea (I) with iodomethane provided S-methylthiouronium iodide (II). This was further condensed with N-methylpiperazine (III) to afford the intermediate piperazine-1-carboxamidine (IV)
| 【1】 Miller, A.A.; Nobbs, M.S.; Hyde, R.M.; Leach, M.J. (Glaxo Wellcome plc); Pharmacologically active CNS cpds.. AU 8945964; EP 0372934; EP 0713703; EP 0715851; EP 0727212; EP 0727213; EP 0727214; JP 1990202876; US 5587380; US 5597828; US 5635507; US 5684005 . |
| 【2】 Patel, R.; Packham, T.W.; Germain, A.L.; Barras, J.R.; Milne, D.J. (GlaxoSmithKline plc); Process of preparing 2,3,5-trihalobenzaldehyde. WO 9507877 . |
合成路线2
该中间体在本合成路线中的序号：(IV)Regioselective lithiation of 1,2,4-trichlorobenzene (V) with n-BuLi at -60 C, followed by quenching of the resultant organolithium compound (VI) with N,N-dimethylformamide yielded 2,3,5-trichlorobenzaldehyde (VII) (1), which was then reduced with NaBH4 to provide alcohol (VIII). Bromination of (VIII) using PBr3 afforded compound (IX), whose bromide atom was displaced with KCN to give the trichlorophenylacetonitrile (X). Claisen condensation of (X) with ethyl formate in the presence of NaOEt furnished the oxo nitrile sodium enolate (XI), which was subsequently O-alkylated with iodomethane yielding the methoxy acrylonitrile (XII). Finally, cyclization of (XII) with the piperazine-1-carboxamidine (IV) in EtOH gave rise to the target pyrimidine derivative
| 【1】 Miller, A.A.; Nobbs, M.S.; Hyde, R.M.; Leach, M.J. (Glaxo Wellcome plc); Pharmacologically active CNS cpds.. AU 8945964; EP 0372934; EP 0713703; EP 0715851; EP 0727212; EP 0727213; EP 0727214; JP 1990202876; US 5587380; US 5597828; US 5635507; US 5684005 . |
| 【2】 Patel, R.; Packham, T.W.; Germain, A.L.; Barras, J.R.; Milne, D.J. (GlaxoSmithKline plc); Process of preparing 2,3,5-trihalobenzaldehyde. WO 9507877 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 62330 | C7H18N4 | 详情 | 详情 | ||
| (V) | 62331 | 1,2,4-trichlorobenzene | C6H3Cl3 | 详情 | 详情 | |
| (VI) | 62332 | (2,3,5-trichlorophenyl)lithium | C6H2Cl3Li | 详情 | 详情 | |
| (VII) | 25670 | 2,3,5-trichlorobenzaldehyde | 56961-75-2 | C7H3Cl3O | 详情 | 详情 |
| (VIII) | 25671 | (2,3,5-trichlorophenyl)methanol | C7H5Cl3O | 详情 | 详情 | |
| (IX) | 25672 | 1-(bromomethyl)-2,3,5-trichlorobenzene | C7H4BrCl3 | 详情 | 详情 | |
| (X) | 25673 | 2-(2,3,5-trichlorophenyl)acetonitrile | C8H4Cl3N | 详情 | 详情 | |
| (XI) | 62333 | sodium (Z)-2-cyano-2-(2,3,5-trichlorophenyl)-1-ethenolate | C9H3Cl3NNaO | 详情 | 详情 | |
| (XII) | 62334 | (E)-3-methoxy-2-(2,3,5-trichlorophenyl)-2-propenenitrile | C10H6Cl3NO | 详情 | 详情 |