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【结 构 式】 
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【分子编号】11016 【品名】1-[5-(Aminocarbonyl)-4-imidazolidinyl]diazonium 【CA登记号】 |
【 分 子 式 】C4H3N5O 【 分 子 量 】137.10092 【元素组成】C 35.04% H 2.21% N 51.08% O 11.67% |
合成路线1
该中间体在本合成路线中的序号：(II)By reaction of 5-diazoimidazole-4-carboxamide (II), prepared by diazotization of 5-aminoimidazole-4-carboxamide (I) with nitrous acid, with methylisocyanate (III) either alone or in dichloromethane.
| 【1】 Stevens, M.F.G.; Baig, G.U.; Triazines and related products, part 22. Synthesis and reactions of imidazo[5,1-c][1,2,4]triazines. J Chem Soc Perkin Trans I. J Chem Soc - Perkins Trans I 1981, 1424. |
| 【2】 Lunt, E.; Stevens, M.F.G.; Stone, R.; Woolbridge, K.R.H. (Cancer Research Campaign Technology Ltd.); Tetrazine derivs., process for their preparation and pharmaceutical compsns. containing them. BE 894175; DE 3231255; FR 2511679; GB 2104522; JP 1983043975; US 5260291 . |
| 【3】 Prous, J.; Castaner, J.; Graul, A.; Temozolomide. Drugs Fut 1994, 19, 8, 746. |
| 【4】 Stevens, M.F.G.; Hickman, J.A.; Stone, R.; Gibson, N.W.; Baig, G.U.; Lunt, E.; Newton, C.G.; Antitumor imidazotetrazinones. 1. Synthesis and chemistry of 8-carbamoyl-3-(2-chloroethyl)imidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one, a novel broad-spectrum antitumor agent. J Med Chem 1984, 27, 196-201, 196. |
合成路线2
该中间体在本合成路线中的序号：(VIII)2) The condensation of N,N-diphenylcarbamoyl chloride (IV) with [13C]-labeled methylamine (V) gives the corresponding urea (VI), which by heating at 240 C is converted to the [13C]-labeled methyl isocyanate (VII). Finally, this compound is cyclized with the diazonium salt (VIII) (obtained by diazotation of 3-aminopyrazole-4-carbonitrile with NaNO2-HCl in the usual way) to afford temozolomide labeled at the methyl in the 3-position. 3) The preceding sequence performed with [15N]-labeled methylamine (X) gives urea (XI), isocyanate (XII) and finally temozolomide labeled at the N in the 3-position.
| 【1】 Wilman, D.E.V.; Thomson, W.; Wheelhouse, R.T.; Stevens, M.F.G.; Antitumour imidazotetrazines. 31. The synthesis of isotopically labelled temozolomide and a multinuclear (H-1, C-13, N-15) magnetic resonance investigation of temozolomide and mitozolomide. J Chem Soc - Perkins Trans I 1995, 3, 3, 249. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VII),(XII) | 11019 | (Methylimino)(oxo)methane; methyl isocyanate | C2H3NO | 详情 | 详情 | |
| (V),(X) | 11021 | Methanamine; Methylamine | 74-89-5 | CH5N | 详情 | 详情 |
| (VI),(XI) | 11022 | 1-Methyl-3,3-diphenylurea; N'-Methyl-N,N-diphenylurea | 13114-72-2 | C14H14N2O | 详情 | 详情 |
| (IV) | 11020 | N,N-Diphenylcarbamic chloride; Diphenylcarbamyl chloride | 83-01-2 | C13H10ClNO | 详情 | 详情 |
| (V) | 45041 | methylamine; methanamine | CH5N | 详情 | 详情 | |
| (VI) | 45042 | N'-methyl-N,N-diphenylurea | C14H14N2O | 详情 | 详情 | |
| (VII) | 45043 | (methylimino)(oxo)methane; methyl isocyanate | C2H3NO | 详情 | 详情 | |
| (VIII) | 11016 | 1-[5-(Aminocarbonyl)-4-imidazolidinyl]diazonium | C4H3N5O | 详情 | 详情 | |
| (IX) | 11015 | 5-Amino-1H-imidazole-4-carboxamide | 360-97-4 | C4H6N4O | 详情 | 详情 |
| (X) | 45044 | methylamine; methanamine | CH5N | 详情 | 详情 | |
| (XI) | 45045 | N'-methyl-N,N-diphenylurea | C14H14N2O | 详情 | 详情 | |
| (XII) | 45046 | methyl isocyanate; (methylimino)(oxo)methane | C2H3NO | 详情 | 详情 |