|
【结 构 式】 
|
【分子编号】29667 【品名】N-(2-chloroethyl)-N-[2-(3-methoxyphenyl)-1-methylethyl]-N-methylamine; N-(2-chloroethyl)-1-(3-methoxyphenyl)-N-methyl-2-propanamine 【CA登记号】 |
【 分 子 式 】C13H20ClNO 【 分 子 量 】241.76064 【元素组成】C 64.59% H 8.34% Cl 14.66% N 5.79% O 6.62% |
合成路线1
该中间体在本合成路线中的序号：(VI)The reaction of ethanolimine (I) with m-methoxyphenylacetone (II) gives the corresponding Schiff base (III), which is reduced with H2 over Pd/C to the corresponding secondary amine (IV). Methylation of (IV) with HCHO-HCOOH yields 1-(m-methoxyphenyl)-2-(N-(2-hydroxyethyl)-N-methylaminoipropane (V), which is treated with SOCl2 to afford the 2-chloroethyl derivative (VI). Finally, this compound is condensed with benzhydrol (VII) by means of NaNH2 in refluxing benzene, and treated with HCl.
| 【1】 Lindner, E.; Ehrhart, G.; Ott, H. (Aventis Pharma AG); m-Methoxy-alpha-methyl-phenethyl-amino-diphenylmethyl ethers. US 3565955 . |
| 【2】 Mannhold, R.; HOE-263. Drugs Fut 1985, 10, 6, 458. |
| 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) | 10259 | Ethanol amine;Ethanolamine;2-Aminoethanol; 2-Amino-1-ethanol；2-Aminoethyl alcohol | 141-43-5 | C2H7NO | 详情 | 详情 |
| (II) | 29663 | 1-(3-methoxyphenyl)acetone | 3027-13-2 | C10H12O2 | 详情 | 详情 |
| (III) | 29664 | 2-[[(E)-2-(3-methoxyphenyl)-1-methylethylidene]amino]-1-ethanol | C12H17NO2 | 详情 | 详情 | |
| (IV) | 29665 | 2-[[2-(3-methoxyphenyl)-1-methylethyl]amino]-1-ethanol | C12H19NO2 | 详情 | 详情 | |
| (V) | 29666 | 2-[[2-(3-methoxyphenyl)-1-methylethyl](methyl)amino]-1-ethanol | C13H21NO2 | 详情 | 详情 | |
| (VI) | 29667 | N-(2-chloroethyl)-N-[2-(3-methoxyphenyl)-1-methylethyl]-N-methylamine; N-(2-chloroethyl)-1-(3-methoxyphenyl)-N-methyl-2-propanamine | C13H20ClNO | 详情 | 详情 | |
| (VII) | 11845 | Diphenylmethanol; Benzhydrol | 91-01-0 | C13H12O | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VII)Esterification of pyrrole-2-carboxylic acid (I) by treatment with TMSCl in MeOH yields methyl carboxylate (II), which is then condensed with tert-butyl chloride (III) by means of AlCl3 in 1,2-dichloroethane to provide methyl 5-tert-butyl pyrrole-2-carboxylate (IV). Nitration of pyrrolic derivative (IV) by reaction with HNO3/H2SO4 affords a mixture of compounds from which 3-nitropyrrole derivative (V) is cromatographically separated. Hydrogenation of (V) over Pd/C in MeOH allows conversion of the nitro group into an amino group to furnish methyl 3-amino-5-tert-butylpyrrole-2-carboxylate (VI), which is finally coupled to 2,3-dichlorophenyl isocyanate (VII) in dichloromethane to afford the desired compound.
| 【1】 Johnson, J.S.; Dally, R.; Redman, A.M.; et al.; p38 Kinase inhibitors for the treatment of arthritis and osteoporosis: Thienyl, furyl, and pyrrolyl ureas. Bioorg Med Chem Lett 2001, 11, 1, 9. |
| 【2】 Gunn, D.; Ranges, G.; Chen, J.; Bombara, M.; Scott, W.; Rauner, D.; Redman, A.; Paulsen, H.; Smith, R.; Renick, J. (Bayer Corp.); Inhibition of p38 kinase activity by aryl ureas. WO 9852558 . |
| 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) | 31796 | Pyrrole-2-carboxylic acid; 1H-pyrrole-2-carboxylic acid | 634-97-9 | C5H5NO2 | 详情 | 详情 |
| (II) | 45616 | methyl 1H-pyrrole-2-carboxylate | C6H7NO2 | 详情 | 详情 | |
| (III) | 47128 | 2-chloro-2-methylpropane | 507-20-0 | C4H9Cl | 详情 | 详情 |
| (IV) | 47129 | methyl 5-(tert-butyl)-1H-pyrrole-2-carboxylate | C10H15NO2 | 详情 | 详情 | |
| (V) | 47130 | methyl 5-(tert-butyl)-3-nitro-1H-pyrrole-2-carboxylate | C10H14N2O4 | 详情 | 详情 | |
| (VI) | 47131 | methyl 3-amino-5-(tert-butyl)-1H-pyrrole-2-carboxylate | C10H16N2O2 | 详情 | 详情 | |
| (VII) | 29667 | N-(2-chloroethyl)-N-[2-(3-methoxyphenyl)-1-methylethyl]-N-methylamine; N-(2-chloroethyl)-1-(3-methoxyphenyl)-N-methyl-2-propanamine | C13H20ClNO | 详情 | 详情 |