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【结 构 式】 
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【分子编号】34071 【品名】2-[[(5-methyl-1H-imidazol-4-yl)methyl]sulfanyl]-1-ethanamine; 2-[[(5-methyl-1H-imidazol-4-yl)methyl]sulfanyl]ethylamine 【CA登记号】 |
【 分 子 式 】C7H13N3S 【 分 子 量 】171.26644 【元素组成】C 49.09% H 7.65% N 24.53% S 18.72% |
合成路线1
该中间体在本合成路线中的序号：(IV)The cyclization of ethyl 2-formyl-3-(3,4-methylenedioxyphenyl)propionate (I) with nitroguanidine (II) by means of sodium methoxide in refluxing methanol gives 2-nitroamino-5-(3,4-methylenedioxybenzyl)-4-pyrimidone (III), which is then condensed with 2-(5-methyl-4-imidazolylmethylthio)ethylamine (IV) in refluxing ethanol.
| 【1】 Brown, T.H. (SmithKline Beecham plc); Process for preparing 2-aminopyrimidones, intermediate 2-nitroaminopyrimidones and a process for their preparation. EP 0004793 . |
| 【2】 Blancafort, P.; Castaner, J.; Serradell, M.N.; Oxmetidine hydrochloride. Drugs Fut 1982, 7, 10, 749. |
| 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) | 37081 | ethyl 3-(1,3-benzodioxol-5-yl)-2-formylpropanoate | C13H14O5 | 详情 | 详情 | |
| (II) | 15496 | nitroguanidine | 556-88-7 | CH4N4O2 | 详情 | 详情 |
| (III) | 37082 | 5-(1,3-Benzodioxol-5-ylmethyl)-2-(nitroamino)-1H-pyrimidin-4-one | 72716-71-3 | C12H10N4O5 | 详情 | 详情 |
| (IV) | 34071 | 2-[[(5-methyl-1H-imidazol-4-yl)methyl]sulfanyl]-1-ethanamine; 2-[[(5-methyl-1H-imidazol-4-yl)methyl]sulfanyl]ethylamine | C7H13N3S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)The cyclization of ethyl 3-(3,4-ethylenedioxyphenyl)propionate (V), ethyl formate (VI) and thiourea (VII) by means of Na in ether and ethanol gives 5-(3,4-methylenedioxyphenyl)-2-thiouracil (VIII), which by reaction with methyl iodide and NaOH in ethanol-water is converted into 5-(3,4-methylenedioxybenzyl)-2-methylthio-4-pyrimidone (IX). Finally, this compound is condensed with (IV) by heating at 150 C.
| 【1】 Brown, T.H.; DE 2660563 . |
| 【2】 Blancafort, P.; Castaner, J.; Serradell, M.N.; Oxmetidine hydrochloride. Drugs Fut 1982, 7, 10, 749. |
| 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) | 34071 | 2-[[(5-methyl-1H-imidazol-4-yl)methyl]sulfanyl]-1-ethanamine; 2-[[(5-methyl-1H-imidazol-4-yl)methyl]sulfanyl]ethylamine | C7H13N3S | 详情 | 详情 | |
| (V) | 37083 | ethyl 3-(1,3-benzodioxol-5-yl)propanoate | C12H14O4 | 详情 | 详情 | |
| (VII) | 10180 | Thiourea | 62-56-6 | CH4N2S | 详情 | 详情 |
| (VIII) | 37084 | 5-(1,3-benzodioxol-5-ylmethyl)-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone | C12H10N2O3S | 详情 | 详情 | |
| (IX) | 37085 | 5-(1,3-benzodioxol-5-ylmethyl)-2-(methylsulfanyl)-4(1H)-pyrimidinone | C13H12N2O3S | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(IV)The reaction of propargylamine (II) with dimethyl cyanoiminodithiocarbonate (III) in refluxing acetonitrile gives N-cyano-N'-propargyl-S-methylisothiourea (IV), which is then condensed with 2-[(5-methyl-4-imidazolyl)methylthio]ethylamine (V) in refluxing methanol.
| 【1】 Crenshaw, R.R.; Luke, G.M. (Bristol-Myers Squibb Co.); Imidazolylmethylthioethyl alkynyl guanidines. US 4112234 . |
| 【2】 Serradell, M.N.; Blancafort, P.; Castaner, J.; Etintidine hydrochloride. Drugs Fut 1982, 7, 10, 732. |
| 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) | 18174 | [[bis(methylsulfanyl)methylene]amino](nitrilo)methane | 10191-60-3 | C4H6N2S2 | 详情 | 详情 |
| (II) | 21408 | 2-propyn-1-amine; 2-propynylamine; 2-propylamine | 2450-71-7 | C3H5N | 详情 | 详情 |
| (III) | 37101 | 3-[[(cyanoimino)(methylsulfanyl)methyl]amino]-1-propyne | C6H7N3S | 详情 | 详情 | |
| (IV) | 34071 | 2-[[(5-methyl-1H-imidazol-4-yl)methyl]sulfanyl]-1-ethanamine; 2-[[(5-methyl-1H-imidazol-4-yl)methyl]sulfanyl]ethylamine | C7H13N3S | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(III)1) By refluxing N-cyano-N',S-dimethylisoithiourea (B) and 5-methyl-4-[(2-aminoethyl)thiomethyl imidazol (III) in acetonitrile. The latter is prepared by reacting cysteamine (A) and 5-methyl-4-(hydroxymethyl)imidazol (II) (from 5-methylimidazol (I) and formalin) in acetic acid, in hydrochloric acid or in hydrobromic acid. 2) By reaction of 5-methyl-4-[(2-aminoethyl)thiomethyl]imidazol (III) with cyanodithioimido carbonic (C) acid dimethyl ester to give the isothiourea (IV), followed by reaction with methylamine. 3) By refluxing 1-methyl-3-[2-[[(5-methylimidazol-4-yl)-methyl]thio]ethyl]-2-thiourea (metiamide) (V) and lead cyanamide. The first is prepared by reaction of 5-methyl-4-[(2-aminoethyl)thiomethyl]imidazol (III) with methyl isocyanate (D).
| 【1】 Durant, G.J.; et al.; Pharmacologically active guanidine compounds. DE 2211454; DE 2265369; FR 2128505; GB 1338169; US 3950333 . |
| 【2】 Erlenmeyer, H.; et al.; Helv Chim Acta 1948, 31, 32. |
| 【3】 Durant, G.J.; et al.; Certain N-cyanoguanidines. DE 2344779; FR 2199467; GB 1397436; JP 49075574; US 3876647 . |
| 【4】 Castaner, J.; Cimetidine. Drugs Fut 1976, 1, 1, 13. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (D) | 12092 | Methyl isothiocyanate; MITC; (Methylimino)(thioxo)methane | 556-61-6 | C2H3NS | 详情 | 详情 |
| (A) | 13186 | 2-Aminoethanethiol; 2-Amino-1-ethanethiol; 2-Aminoethylhydrosulfide; Cysteamine | 60-23-1 | C2H7NS | 详情 | 详情 |
| (B) | 34072 | [[(E)-(methylamino)(methylsulfanyl)methylidene]amino](nitrilo)methane | C4H7N3S | 详情 | 详情 | |
| (I) | 34070 | 5-methyl-1H-imidazole | 822-36-6 | C4H6N2 | 详情 | 详情 |
| (II) | 14216 | (5-Methyl-1H-imidazol-4-yl)methanol | 29636-87-1 | C5H8N2O | 详情 | 详情 |
| (III) | 34071 | 2-[[(5-methyl-1H-imidazol-4-yl)methyl]sulfanyl]-1-ethanamine; 2-[[(5-methyl-1H-imidazol-4-yl)methyl]sulfanyl]ethylamine | C7H13N3S | 详情 | 详情 | |
| (IV) | 34073 | 4-[[(2-[[(cyanoimino)(methylsulfanyl)methyl]amino]ethyl)sulfanyl]methyl]-5-methyl-1H-imidazole | C10H15N5S2 | 详情 | 详情 | |
| (V) | 34074 | N-methyl-N'-(2-[[(5-methyl-1H-imidazol-4-yl)methyl]sulfanyl]ethyl)thiourea | C9H16N4S2 | 详情 | 详情 | |
| (C) | 18174 | [[bis(methylsulfanyl)methylene]amino](nitrilo)methane | 10191-60-3 | C4H6N2S2 | 详情 | 详情 |