|
【结 构 式】 
|
【分子编号】28758 【品名】1-iodopropane 【CA登记号】107-08-4 |
【 分 子 式 】C3H7I 【 分 子 量 】169.99305 【元素组成】C 21.2% H 4.15% I 74.65% |
合成路线1
该中间体在本合成路线中的序号：(V)The partial alcoholysis of 2-cyanomethyl-1,4-benzodioxane (I) with ethanol and HCl in ether gives ethyl-(1,4-benzodioxan-2-yl)acetimidate (II), which is cyclized with aminoacetaldehyde diethylketal (III) in refluxing ethanol yielding 2-[(1,4-benzodioxan-2-yl)methyl]imidazole (IV). Finally, this compound is alkylated with ethyl iodide (V) and NaH in DMF.
| 【1】 Caroon, J.M.; et al.; Structure-activity relationships for 2-substituted imidazoles as alpha2-adrenoceptor antagonists. J Med Chem 1982, 25, 6, 666-670. |
| 【2】 Kluge, A.F.; Strosberg, A.M.; Whiting, R.; Christie, G. (Syntex (USA), Inc.); 2-(1,4-Benzodioxan-2-ylalkyl)miidazoles useful as antidepressants. EP 0047531; JP 57050989; US 4302469 . |
| 【3】 Castaner, J.; Serradell, M.N.; Imiloxan. Drugs Fut 1986, 11, 2, 108. |
| 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) | 28755 | 2-(2,3-dihydro-1,4-benzodioxin-2-yl)acetonitrile | C10H9NO2 | 详情 | 详情 | |
| (II) | 28756 | ethyl 2-(2,3-dihydro-1,4-benzodioxin-2-yl)ethanimidoate | C12H15NO3 | 详情 | 详情 | |
| (III) | 10331 | 2,2-Diethoxy-1-ethanamine; 2,2-Diethoxyethylamine; Aminoacetaldehyde diethyl acetal | 645-36-3 | C6H15NO2 | 详情 | 详情 |
| (IV) | 28757 | 2-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-1H-imidazole | C12H12N2O2 | 详情 | 详情 | |
| (V) | 28758 | 1-iodopropane | 107-08-4 | C3H7I | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)The reaction of dihydrolysergol (I) with propyl iodide (II) in hot sulfolane gives the quaternary salt (III), which is treated with Na2S in the same solvent, yielding the propyl derivative (IV). The reaction of (IV) with mesyl chloride and pyridine affords the corresponding mesylate (V), which is finally treated with commercial Na-S-CH3 in DMF to afford the target methylsulfanyl derivative.
| 【1】 Anastasia, L.; et al.; Simple and selective one-pot replacement of the N-methyl group of tertiary amines by quaternization and demethylation with sodium sulfide or potassium thioacetate: An application to the synthesis of pergolide. J Chem Soc - Perkins Trans I 2001, 19, 2398. |
| 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) | 10051 | [(6aR,9R,10aR)-7-methyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinolin-9-yl]methanol; 9,10-Dyhydrosergol | 18051-16-6 | C16H20N2O | 详情 | 详情 |
| (II) | 28758 | 1-iodopropane | 107-08-4 | C3H7I | 详情 | 详情 |
| (III) | 54917 | (6aR,9R,10aR)-9-(hydroxymethyl)-7-methyl-7-propyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinolin-7-ium iodide | C19H27IN2O | 详情 | 详情 | |
| (IV) | 32242 | [(6aR,9R,10aR)-7-propyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinolin-9-yl]methanol; 6-n-Propyl-8beta-hydroxymethylergoline | C18H24N2O | 详情 | 详情 | |
| (V) | 54918 | [(6aR,9R,10aR)-7-propyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinolin-9-yl]methyl methanesulfonate | C19H26N2O3S | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：L-Picolinic acid (II) is protected with benzyl chloroformiate (VII) to afford compound (VIII), which is condensed with 2-methylaniline (IX) by means SOCl2/DMAP to yield amide (X). This compound (X) is methylated by treatment with palladium acetate (Pd(Oac)2) to obtain compound (XI), which is deprotected by means HBr to yield compound (V). Finally, this compound (V) is alkylated with 1-iodopropane by means potassium carbonate (K2CO3) to yield Ropivacaine.
| 【1】 Sandeberg, R.V. (AstraZeneca plc); S-(-)-1-propyl-2',6'-pipecoloxylidide hydrochloride monohydrate, process for its preparation and pharmaceutical preparation containing it. EP 0239710; US 4870086 . |
| 【2】 T. af Ekenstam, B.; Bovin, C. (Alpharma Inc.); L-N-n-Propylpipecolic acid-2,6-xylidide and method for preparing the same. JP 1985502054; WO 8500599 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 28758 | 1-iodopropane | 107-08-4 | C3H7I | 详情 | 详情 | |
| (II) | 17380 | (2S)hexahydro-2-pyridinecarboxylic acid; (S)-pipecolic acid | 3105-95-1 | C6H11NO2 | 详情 | 详情 |
| (V) | 17531 | (2S)-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide | C14H20N2O | 详情 | 详情 | |
| (VII) | 10101 | Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene | 501-53-1 | C8H7ClO2 | 详情 | 详情 |
| (VIII) | 19504 | (2S)-1-[(benzyloxy)carbonyl]-2-piperidinecarboxylic acid | C14H17NO4 | 详情 | 详情 | |
| (IX) | 15511 | o-toluidine; 2-methylphenylamine;2-Methylaniline；2-Aminotoluene;1-Amino-2-methylbenzene;1-Methyl-2-aminobenzene; ortho-Toluidine | 95-53-4 | C7H9N | 详情 | 详情 |
| (X) | 19506 | benzyl (2S)-2-(2-toluidinocarbonyl)-1-piperidinecarboxylate | C21H24N2O3 | 详情 | 详情 | |
| (XI) | 19507 | benzyl (2S)-2-[(2,6-dimethylanilino)carbonyl]-1-piperidinecarboxylate | C22H26N2O3 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：Compound (XII) is protected with benzyl chloroformiate (VII) to afford compound (XIII), which is condensed with 2,5-dimethylaniline (XIV) by means SOCl2/DMAP to yield amide (XIV). This compound (XIV) is deprotected by means trimethylsillyl chloride to yield compound (XV), which is hydrogenated by means Rh/Al2O3. Finally, this compound (V) is alkylated with 1-iodopropane by means potassium carbonate (K2CO3) to yield Ropivacaine.
| 【1】 T. af Ekenstam, B.; Bovin, C. (Alpharma Inc.); L-N-n-Propylpipecolic acid-2,6-xylidide and method for preparing the same. JP 1985502054; WO 8500599 . |
| 【2】 Sandeberg, R.V. (AstraZeneca plc); S-(-)-1-propyl-2',6'-pipecoloxylidide hydrochloride monohydrate, process for its preparation and pharmaceutical preparation containing it. EP 0239710; US 4870086 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 28758 | 1-iodopropane | 107-08-4 | C3H7I | 详情 | 详情 | |
| (IV) | 17527 | 2,6-Xylidine; 2,6-Dimethylaniline; 2,6-Dimethylphenylamine | 87-62-7 | C8H11N | 详情 | 详情 |
| (V) | 17531 | (2S)-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide | C14H20N2O | 详情 | 详情 | |
| (VII) | 10101 | Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene | 501-53-1 | C8H7ClO2 | 详情 | 详情 |
| (XII) | 19508 | (2S)-1,2,3,4-tetrahydro-2-pyridinecarboxylic acid | C6H9NO2 | 详情 | 详情 | |
| (XIII) | 19509 | (2S)-1-[(benzyloxy)carbonyl]-1,2,3,4-tetrahydro-2-pyridinecarboxylic acid | C14H15NO4 | 详情 | 详情 | |
| (XIV) | 19510 | benzyl (2S)-2-[(2,6-dimethylanilino)carbonyl]-3,4-dihydro-1(2H)-pyridinecarboxylate | C22H24N2O3 | 详情 | 详情 | |
| (XV) | 19511 | (2S)-N-(2,6-dimethylphenyl)-1,2,3,4-tetrahydro-2-pyridinecarboxamide | C14H18N2O | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(IV)The reaction of 3-methoxyphenylethylamine (I) with phenylethyl bromide (II) in refluxing triethylamine gives 3-methoxy-N-(phenylethyl)phenylethylamine (III), which is alkylated with 1-iodopropane by means of K2CO3 in refluxing acetone yielding 3-methoxy-N-propyl-N-(phenylethyl)phenylethylamine (IV). Finally, this compound is demethylated by treatment with refluxing aqueous 48% HBr and formation of the HCl salt with hydrochloric acid.
| 【1】 Nedelec, L.; et al.; Synthesis of study of the dopaminergic activity of di(phenylethyl)amine derivatives. Eur J Med Chem - Chim Ther 1978, 13, 6, 553-556. |
| 【2】 Serradell, M.N.; Castañer, J.; Blancafort, P.; Owen, R.T.; RU-24213. Drugs Fut 1981, 6, 4, 237. |
| 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) | 37185 | 2-(3-methoxyphenyl)-1-ethanamine; 3-methoxyphenethylamine | 2039-67-0 | C9H13NO | 详情 | 详情 |
| (II) | 20730 | 1-(2-bromoethyl)benzene；1-Bromo-2-phenylethane;(2-Bromoethyl)benzene;Phenethyl bromide | 103-63-9 | C8H9Br | 详情 | 详情 |
| (III) | 37186 | N-(3-methoxyphenethyl)-N-phenethylamine; 2-(3-methoxyphenyl)-N-phenethyl-1-ethanamine | C17H21NO | 详情 | 详情 | |
| (IV) | 28758 | 1-iodopropane | 107-08-4 | C3H7I | 详情 | 详情 |
| (V) | 37187 | N-(3-methoxyphenethyl)-N-phenethyl-N-propylamine; N-(3-methoxyphenethyl)-N-phenethyl-1-propanamine | C20H27NO | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：Alkylation of adenosine-2-thione (I) with iodopropane produced the propylthioether (II). Subsequent treatment with phosphoryl chloride in triethyl phosphate, followed by aqueous work-up afforded (propylthio)adenylic acid (III). Then, after activation with carbonyldiimidazole, the condensation of (III) with difluoromethylenebisphosphonic acid (IV) generated the target anhydride.
| 【1】 Ingall, A.H.; Cage, P.A. (Celltech Medeva plc); ATP analogues. EP 0508687; US 5654285 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 28758 | 1-iodopropane | 107-08-4 | C3H7I | 详情 | 详情 | |
| (I) | 28113 | 6-amino-9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-3,9-dihydro-2H-purine-2-thione | C10H13N5O4S | 详情 | 详情 | |
| (II) | 22302 | (2R,3R,4S,5R)-2-[6-amino-2-(propylsulfanyl)-9H-purin-9-yl]-5-(hydroxymethyl)tetrahydro-3,4-furandiol | C13H19N5O4S | 详情 | 详情 | |
| (III) | 22303 | [(2R,3S,4R,5R)-5-[6-amino-2-(propylsulfanyl)-9H-purin-9-yl]-3,4-dihydroxytetrahydro-2-furanyl]methyl dihydrogen phosphate | C13H20N5O7PS | 详情 | 详情 | |
| (IV) | 28114 | difluoro(phosphono)methylphosphonic acid | CH4F2O6P2 | 详情 | 详情 |