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RPR-110754((-)-enantiomer), RPR-110750((+)-enantiomer), RPR-104632

2H-1,2,4-苯并噻二嗪-3-羧酸,2-[(3-溴苯基)甲基]-6,8-二氯-3,4-二氢-,1,1-二氧化物Chemical Name: 2-(3-Bromobenzyl)-6,8-dichloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-3-carboxylic acid 1,1-dioxide
CAS No. 154106-92-0
项目整合开发状态: Preclinical
项目研究机构: Aventis Pharma (Originator)
合成路线:This compound has been obtained by two related ways:1) The sulfonation of 3,5-dichloroaniline (I) with chlorosulfonic acid gives 2-amino-4,6-dichlorobenzenesulfonyl chloride (II),which is condensed with 3-bromobenzylamine (III) by means of TEA yielding the corresponding sulfonamide (IV).The cyclization of (IV) with glyoxylic acid (A) in ethanol/sulfuric acid affords the esterified benzothiadiazine-3-carboxylate (V),which is finally hydrolyzed with aqueous NaOH.2) The reaction of sulfonyl chloride (II) with liquid ammonia gives the corresponding sulfonamide (VI),which is cyclized with glyoxylic acid (A) as before yielding the benzothiadiazine (VII).Finally the alkylation of (VII) with 3-bromobenzyl bromide (VIII) by means of NaH affords the already reported benzothiadiazine-3-carboxylate (V).3) The enantiomers of the title compound have been obtained in optically pure form by preparative liquid chromatography on a Pirkle-type chiral phase column.
📌 参考资料/链接:
参考文献标题:RPR 104632,a novel antagonist at the glycine site of the N-methyl-D-aspartate receptor-channel complex
文献作者:Doble,A.; Boireau,A.; et al.
参考来源:Can J Physiol Pharmacol 1994,72(Suppl.1),333

📄 详细内容


合成路线:This compound has been obtained by two related ways:1) The sulfonation of 3,5-dichloroaniline (I) with chlorosulfonic acid gives 2-amino-4,6-dichlorobenzenesulfonyl chloride (II),which is condensed with 3-bromobenzylamine (III) by means of TEA yielding the corresponding sulfonamide (IV).The cyclization of (IV) with glyoxylic acid (A) in ethanol/sulfuric acid affords the esterified benzothiadiazine-3-carboxylate (V),which is finally hydrolyzed with aqueous NaOH.2) The reaction of sulfonyl chloride (II) with liquid ammonia gives the corresponding sulfonamide (VI),which is cyclized with glyoxylic acid (A) as before yielding the benzothiadiazine (VII).Finally the alkylation of (VII) with 3-bromobenzyl bromide (VIII) by means of NaH affords the already reported benzothiadiazine-3-carboxylate (V).3) The enantiomers of the title compound have been obtained in optically pure form by preparative liquid chromatography on a Pirkle-type chiral phase column.

参考文献标题:Synthesis and SAR of 2H-1,2,4-benzothiadiazine-1,1-dioxide-3-carboxylic acid derivatives as novel potent glycine antagonists of the NMDA receptor-channel complex
文献作者:Jimonet,P.; et al.
参考来源:Bioorg Med Chem Lett 1994,4(23),2735


合成路线:This compound has been obtained by two related ways:1) The sulfonation of 3,5-dichloroaniline (I) with chlorosulfonic acid gives 2-amino-4,6-dichlorobenzenesulfonyl chloride (II),which is condensed with 3-bromobenzylamine (III) by means of TEA yielding the corresponding sulfonamide (IV).The cyclization of (IV) with glyoxylic acid (A) in ethanol/sulfuric acid affords the esterified benzothiadiazine-3-carboxylate (V),which is finally hydrolyzed with aqueous NaOH.2) The reaction of sulfonyl chloride (II) with liquid ammonia gives the corresponding sulfonamide (VI),which is cyclized with glyoxylic acid (A) as before yielding the benzothiadiazine (VII).Finally the alkylation of (VII) with 3-bromobenzyl bromide (VIII) by means of NaH affords the already reported benzothiadiazine-3-carboxylate (V).3) The enantiomers of the title compound have been obtained in optically pure form by preparative liquid chromatography on a Pirkle-type chiral phase column.

参考文献标题:2H-3,4-Dihydro-1,2,4-benzothiadiazine-1,1-dioxide-3-carboxylic acid derivatives,a novel family of glycine antagonists of the NMDA receptor channel complex
文献作者:Mignani,S.; et al.
参考来源:Drugs Fut 1995,20(11),1133


合成路线:This compound has been obtained by two related ways:1) The sulfonation of 3,5-dichloroaniline (I) with chlorosulfonic acid gives 2-amino-4,6-dichlorobenzenesulfonyl chloride (II),which is condensed with 3-bromobenzylamine (III) by means of TEA yielding the corresponding sulfonamide (IV).The cyclization of (IV) with glyoxylic acid (A) in ethanol/sulfuric acid affords the esterified benzothiadiazine-3-carboxylate (V),which is finally hydrolyzed with aqueous NaOH.2) The reaction of sulfonyl chloride (II) with liquid ammonia gives the corresponding sulfonamide (VI),which is cyclized with glyoxylic acid (A) as before yielding the benzothiadiazine (VII).Finally the alkylation of (VII) with 3-bromobenzyl bromide (VIII) by means of NaH affords the already reported benzothiadiazine-3-carboxylate (V).3) The enantiomers of the title compound have been obtained in optically pure form by preparative liquid chromatography on a Pirkle-type chiral phase column.

参考文献标题:Neuroprotective effects of RPR 104632,a novel antagonist at the glycine site of the NMDA receptor,in vitro
文献作者:Burgevin,M.C.; Boireau,A.; Malgouris,C.; Peny,C.; Durand,G.; Bordier,F.; Meunier,M.; Miquet,J.M.; Daniel,M.; Chevet,T.; Jimonet,P.; Mignani,S.; Blanchard,J.C.; Doble,A.
参考来源:Eur J Pharmacol 1996,300(3),237


合成路线:This compound has been obtained by two related ways:1) The sulfonation of 3,5-dichloroaniline (I) with chlorosulfonic acid gives 2-amino-4,6-dichlorobenzenesulfonyl chloride (II),which is condensed with 3-bromobenzylamine (III) by means of TEA yielding the corresponding sulfonamide (IV).The cyclization of (IV) with glyoxylic acid (A) in ethanol/sulfuric acid affords the esterified benzothiadiazine-3-carboxylate (V),which is finally hydrolyzed with aqueous NaOH.2) The reaction of sulfonyl chloride (II) with liquid ammonia gives the corresponding sulfonamide (VI),which is cyclized with glyoxylic acid (A) as before yielding the benzothiadiazine (VII).Finally the alkylation of (VII) with 3-bromobenzyl bromide (VIII) by means of NaH affords the already reported benzothiadiazine-3-carboxylate (V).3) The enantiomers of the title compound have been obtained in optically pure form by preparative liquid chromatography on a Pirkle-type chiral phase column.
参考文献标题:Synthesis of potential diuretic agents.II.Dichloro-derivatives of 1,2,4-benzothiadiazine-1,1-dioxide
文献作者:Shot,J.H.; Biermacher,U.
参考来源:J Am Chem Soc 1960,21135-38


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