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【结 构 式】

【分子编号】17285

【品名】L-ornithine

【CA登记号】70-26-8

【 分 子 式 】C5H12N2O2

【 分 子 量 】132.16256

【元素组成】C 45.44% H 9.15% N 21.2% O 24.21%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(III)

546C88 has been obtained by several related ways: 1) The reaction of N-methylthiourea (I) with methyl iodide gives N,S-dimethylisothiouronium iodide (II), which is then condensed with L-ornithine (III) by means of NaOH or copper acetate. 2) The oxidation of N-methylthiourea (I) with peracetic acid in acetic acid gives N-methylamidinosulfonic acid (IV), which is then condensed with L-ornithine (III) by means of K2CO3 in water. 3) The reaction of cyanogen bromide (V) with methylamine (VI) by means of Na2CO3 in THF gives N-methylcyanamide (VII), which is condensed with pyrazole (VIII) by means of HCl in refluxing dioxane to yield N1-methylpyrazole-1-carboxamidine (IX). Finally, this compound is condensed with L-ornithine (III) by means of LiOH in water. 4) The reaction of cellulose (X) with cyanogen bromide (V) by means of K2CO3 in water/DMF gives the corresponding polymeric cyanate ester (XI), which is condensed with methylamine (VI) to yield the polymeric N-methylamidino compound (XII). Finally, this compound is condensed with L-ornithine (III) by means of CuCO3 in water.

1 Patthy, A.; Bajusz, S.; Patthy, L.; Preparation and characterization of NG-mono-, di- and trimethylated arginines. Acta Biochim Biophys Acad Sci Hung 1977, 12, 3, 191-6.
2 Wroblewski, T.; Castañer, J.; Prous, J.R.; 546C88. Drugs Fut 1998, 23, 2, 123.
3 Dowd, P.; Zhang, W.; Hershline, R.; A highly efficient preparation of NG-methyl-L-arginine and NG-methyl-D-arginine. Synth Commun 1994, 24, 19, 2789-92.
4 Reporter, M.; Corbin, J.L.; A convenient preparation of NG-methylarginine. Anal Biochem 1974, 57, 1, 310-2.
5 Pundak, S.; Wilchek, M.; Synthesis of guanidino-N-alkylarginines by the use of polymeric pseudoureas. J Org Chem 1981, 46, 808-9.
6 Hodson, H.F. (Glaxo Wellcome plc); NG-Monomethyl-L-arginine hydrochloride derivs. and their use in the treatment of septic shock. EP 0651741; JP 1995509239; US 5767312; WO 9402453 .
7 Gillies, I. (Glaxo Wellcome plc); Process for the preparation of NG-monomethyl-L-arginine hydrochloride. WO 9730972 .
8 Patel, R.; Mahal, A.S.; Burford, D.L.W. (Glaxo Wellcome plc); Process for preparing NG-monoalkyl-L-arginine and related cpds. WO 9426701 .
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) 17283 N-methylthiourea 598-52-7 C2H6N2S 详情 详情
(II) 17284 (methylamino)(methylsulfanyl)methaniminium iodide C3H9IN2S 详情 详情
(III) 17285 L-ornithine 70-26-8 C5H12N2O2 详情 详情
(IV) 17286 imino(methylamino)methanesulfonic acid C2H6N2O3S 详情 详情
(VII) 17287 N-methylcyanamide C2H4N2 详情 详情
(VIII) 17288 Pyrazole; 1H-pyrazole 288-13-1 C3H4N2 详情 详情
(IX) 17289 N-methyl-1H-pyrazole-1-carboximidamide C5H8N4 详情 详情
(XII) 17290 [[hydroxy(imino)methyl]amino]methane C2H6N2O 详情 详情

合成路线2

该中间体在本合成路线中的序号:(III)

5) The reaction of L-ornithine (III) with benzaldehyde by means of LiOH gives Ndelta-benzylidene-L-ornitine (XIII), which is treated first with benzyl chloroformate and NaOH and hydrolyzed with HCl to afford Nalpha-(benzyloxycarbonyl)-L-ornithine (XIV). The condensation of (XIV) with N,S-dimethylisothiouronium iodide (II) by means of NaOH gives Nalpha-(benzyloxycarbonyl)-Nomega-methyl-L-arginine (XV), which is finally deprotected by hydrogenation with H2 over Pd/C.

1 Sala, A.; Ferrario, F.; Trupiano, F.; Levi, S.; Multigram synthesis of NG-methyl-(L-)-arginine and its analytical characterization. Synth Commun 1991, 21, 99-105.
2 Wroblewski, T.; Castañer, J.; Prous, J.R.; 546C88. Drugs Fut 1998, 23, 2, 123.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(II) 17284 (methylamino)(methylsulfanyl)methaniminium iodide C3H9IN2S 详情 详情
(III) 12034 4-Chlorophenylamine; 4-Chloroaniline; p-Chloroaniline 106-47-8 C6H6ClN 详情 详情
(III) 17285 L-ornithine 70-26-8 C5H12N2O2 详情 详情
(XIII) 17291 (2S)-2-amino-5-[[(E)-benzylidene]amino]pentanoic acid C12H16N2O2 详情 详情
(XIV) 17292 (2S)-5-amino-2-[[(benzyloxy)carbonyl]amino]pentanoic acid C13H18N2O4 详情 详情
(XV) 17293 (2S)-2-[[(benzyloxy)carbonyl]amino]-5-[[imino(methylamino)methyl]amino]pentanoic acid C15H22N4O4 详情 详情
Extended Information