Targinine hydrochloride, L-NMMA.HCl, L-NMA.HCl, 546C88

合成路线: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.

参考文献标题:Process for preparing NG-monoalkyl-L-arginine and related cpds
文献作者:Patel,R.; Mahal,A.S.; Burford,D.L.W.(Glaxo Wellcome plc)
参考来源:WO 9426701


合成路线: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.

参考文献标题:Process for the preparation of NG-monomethyl-L-arginine hydrochloride
文献作者:Gillies,I.(Glaxo Wellcome plc)
参考来源:WO 9730972


合成路线: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.

参考文献标题:A highly efficient preparation of NG-methyl-L-arginine and NG-methyl-D-arginine
文献作者:Dowd,P.; Zhang,W.; Hershline,R.
参考来源:Synth Commun 1994,24(19),2789-92


合成路线: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.

合成路线: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.

参考文献标题:546C88
文献作者:Wroblewski,T.; Castar,J.; Prous,J.R.
参考来源:Drugs Fut 1998,23(2),123


合成路线: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.

参考文献标题:Synthesis of guanidino-N-alkylarginines by the use of polymeric pseudoureas
文献作者:Pundak,S.; Wilchek,M.
参考来源:J Org Chem 1981,46808-9


合成路线: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.

参考文献标题:A convenient preparation of NG-methylarginine
文献作者:Corbin,J.L.; Reporter,M.
参考来源:Anal Biochem 1974,57(1),310-2