- Production Method of Lamotrigine
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(CAS NO.: ), with its systematic name of 1,2,4-Triazine-3,5-diamine, 6-(2,3-dichlorophenyl)-, could be produced through many synthetic methods.
Following are some of the synthesis routes:
Route one: The Grignard condensation of 2,3-dichloroiodobenzene (I) with CO2 in the presence of Mg / ether gives 2,3-dichlorobenzoic acid (II), which is converted to the corresponding acyl chloride (III) by refluxing with SOCl2.The reaction of (III) with cuprous cyanide and KI in refluxing xylene yields 2,3-dichlorobenzoyl cyanide (IV). Finally, this compound is cyclized with aminoguanidine (V) in DMSO.Route two: ation of 2,3-dichloronitrobenzene (I) with H2 over Ra-Ni in methanol gives 2,3-dichloroaniline (II), which is diazotized with NaNO2 and HCl and treated with CuCN to yield 2,3-dichlorobenzonitrile (III). Hydrolysis of the nitrile (III) with NaOH in refluxing methanol/water affords 2,3-dichlorobenzoic acid (IV), which is treated with hot SOCl2 to provide the corresponding acyl chloride (V). Reaction of (V) with CuCN and KI in refluxing chlorobenzene gives 2,3-dichlorobenzoyl cyanide (VI), which is condensed with aminoguanidine (VII) by means of H2SO4/TsOH in hot toluene to produce 2,3-dichlorobenzoyl cyanide amidinohydrazone (VIII). At last, this compound is cyclized by treatment with NaOMe in refluxing methanol.
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