2,3-dichlorobenzoic acid -Drug Synthesis Database

【结构式】

【分子编号】24007

【品名】2,3-dichlorobenzoic acid

【CA登记号】50-45-3

【分子式】C₇H₄Cl₂O₂

【分子量】191.01296

【元素组成】C 44.02% H 2.11% Cl 37.12% O 16.75%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(II)

The Grignard condensation of 2,3-dichloroiodobenzene (I) with CO2 by means 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.

参考文献中间体

合成目标

【1】 Baxter, M.G.; Elphick, A.R.; Miller, A.A.; Sawyer, D.A. (Glaxo Wellcome plc); 1,2,4-Triazine derivs., process for preparing such cpds., pharmaceutical compsns. and intermediates utilized for this process. CA 1133938; EP 0021121 .
【2】 Castaner, J.; Prous, J.; Lamotrigine. Drugs Fut 1986, 11, 6, 456.

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)	24006	1,2-dichloro-3-iodobenzene	2401-21-0	C₆H₃Cl₂I	详情	详情
(II)	24007	2,3-dichlorobenzoic acid	50-45-3	C₇H₄Cl₂O₂	详情	详情
(III)	24008	2,3-dichlorobenzoyl chloride	2905-60-4	C₇H₃Cl₃O	详情	详情
(IV)	24009	2-(2,3-dichlorophenyl)-2-oxoacetonitrile; 2,3-Dichlorobenzoylcyanide	77668-42-9	C₈H₃Cl₂NO	详情	详情
(V)	10015	1-Hydrazinecarboximidamide; Hydrazinecarboximidamide	79-17-4	CH₆N₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

Hydrogenation 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 yield 2,3-dichlorobenzoyl cyanide amidinohydrazone (VIII). Finally, this compound is cyclized by treatment with NaOMe in refluxing methanol.

参考文献中间体

合成目标

【1】 Srivastava, A.R.; Sasikumar, T.M.; Radhakrishnan, T.V. (RPG Life Sciences Ltd); A process for the preparation of 6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine, commonly known as lamotrigine. WO 0149669 .

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)	52655	2,3-Dichloronitrobenzene; 1,2-Dichloro-3-Nitrobenzene; Nitro-o-dichlorobenzene	3209-22-1	C₆H₃Cl₂NO₂	详情	详情
(II)	28562	2,3-dichlorophenylamine	608-27-5	C₆H₅Cl₂N	详情	详情
(III)	30204	2,3-dichlorobenzonitrile	6574-97-6	C₇H₃Cl₂N	详情	详情
(IV)	24007	2,3-dichlorobenzoic acid	50-45-3	C₇H₄Cl₂O₂	详情	详情
(V)	24008	2,3-dichlorobenzoyl chloride	2905-60-4	C₇H₃Cl₃O	详情	详情
(VI)	24009	2-(2,3-dichlorophenyl)-2-oxoacetonitrile; 2,3-Dichlorobenzoylcyanide	77668-42-9	C₈H₃Cl₂NO	详情	详情
(VII)	10015	1-Hydrazinecarboximidamide; Hydrazinecarboximidamide	79-17-4	CH₆N₄	详情	详情
(VIII)	52654	2-[cyano(phenyl)methylidene]-1-hydrazinecarboximidamide		C₉H₉N₅	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

The reaction of 2,3-dichlorobenzoic acid (I) with oxalyl chloride in dichloromethane gives the acyl chloride (II), which is condensed with labeled copper cyanide (III) by means of KI in refluxing xylene to yield the 2,3-dichlorobenzoyl cyanide (IV). The condensation of (IV) with labeled aminoguanidine (V) by means of sulfuric acid in acetonitrile/water affords adduct (VI), which is finally cyclized by refluxing under the conditions of the preceding reaction to provide the target labeled diaminotriazine. The intermediate labeled copper cyanide (III) has been obtained by reaction of CuSO4 with labeled potassium cyanide (VII) and Na2S2O5 in hot water. The intermediate labeled aminoguanidine (V) has been obtained by methylation of thiourea (VIII) with dimethyl sulfate in boiling water to give S-methylisothiourea (IX), which is finally treated with hydrazine (X) and NaOH in water.

参考文献中间体

合成目标

【1】 Manning, C.O.; et al.; Synthesis of stable isotopically labelled versions of lamotrigine and its methylated metabolite. J Label Compd Radiopharm 2002, 45, 7, 611.

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)	24007	2,3-dichlorobenzoic acid	50-45-3	C₇H₄Cl₂O₂	详情	详情
(II)	24008	2,3-dichlorobenzoyl chloride	2905-60-4	C₇H₃Cl₃O	详情	详情
(III)	56856	Copper (I) cyanide; Cuprous cyanide	544-92-3	CCuN	详情	详情
(III)	56861	cyanocopper		CCuN	详情	详情
(IV)	24009	2-(2,3-dichlorophenyl)-2-oxoacetonitrile; 2,3-Dichlorobenzoylcyanide	77668-42-9	C₈H₃Cl₂NO	详情	详情
(IV)	56862	2-(2,3-dichlorophenyl)-2-oxoacetonitrile		C₈H₃Cl₂NO	详情	详情
(V)	56857			CH₆N₄	详情	详情
(V)	56866			CH₆N₄	详情	详情
(VI)	56858	1,2-dichloro-3-{cyano[(Z)-2-(diaminomethylene)hydrazono]methyl}benzene		C₉H₇Cl₂N₅	详情	详情
(VI)	56867	1,2-dichloro-3-{cyano[(Z)-2-(diaminomethylene)hydrazono]methyl}benzene		C₉H₇Cl₂N₅	详情	详情
(VII)	56859	Potassium cyanide	151-50-8	CKN	详情	详情
(VII)	56860	cyanopotassium		CKN	详情	详情
(VIII)	10180	Thiourea	62-56-6	CH₄N₂S	详情	详情
(VIII)	56863	thiourea		CH₄N₂S	详情	详情
(IX)	10272	[[Amino(imino)methyl]sulfanyl]methane	2986-19-8	C₂H₆N₂S	详情	详情
(IX)	56864	{[amino(imino)methyl]sulfanyl}methane		C₂H₆N₂S	详情	详情
(X)	27344	hydrazine	302-01-2	H₄N₂	详情	详情
(X)	56865	hydrazine		H₄N₂	详情	详情

Extended Information