SB-204070
1,4-苯并二恶英-5-羧酸,8-氨基-7-氯-2,3-二氢,(1-丁基-4-哌啶基)甲酯Chemical Name: 8-Amino-7-chloro-1,4-benzodioxan-5-carboxylic acid 1-butylpiperidin-4-ylmethyl ester
CAS No. 148702-58-3
项目整合开发状态: Preclinical
项目研究机构: GlaxoSmithKline (Originator)
合成路线:The chlorination of 8-acetamido-2,3-dihydro-1,4-benzodioxin-5-carboxylic acid (I) with chlorine in acetic acid gives the 7-chloro derivative (II),which is treated with aqueous NaOH to yield 8-amino-2,3-dihydro-1,4-benzodioxin-5-carboxylic acid (III).The reaction of (III) with carbonyldiimidazole (CDI) affords the activated intermediate (IV),which is finally condensed with 1-(1-butylpiperidin-4-yl)methanol (V) by means of MeLi in THF.The intermediate 1-(1-butylpiperidin-4-yl)methanol (V) has been obtained by condensation of piperidine-4-carboxylic acid ethyl ester (VI) with 1-bromobutane (VII) by means of K2CO3 in methanol,followed by reduction of the ester group with LiAlH4 in THF.
📌 参考资料/链接：
参考文献标题:Substituted 2,3-alkylenedioxybenzamides
文献作者:Bulteau,G.; Acher,J.; Thominet,M.; Collignon,C.(Ile de France)
参考来源:DE 2734270; FR 2360305; GB 1571278; GB 1571447; JP 53018570; US 4186135; US 4248885; US 4255580
📄 详细内容
合成路线:The chlorination of 8-acetamido-2,3-dihydro-1,4-benzodioxin-5-carboxylic acid (I) with chlorine in acetic acid gives the 7-chloro derivative (II),which is treated with aqueous NaOH to yield 8-amino-2,3-dihydro-1,4-benzodioxin-5-carboxylic acid (III).The reaction of (III) with carbonyldiimidazole (CDI) affords the activated intermediate (IV),which is finally condensed with 1-(1-butylpiperidin-4-yl)methanol (V) by means of MeLi in THF.The intermediate 1-(1-butylpiperidin-4-yl)methanol (V) has been obtained by condensation of piperidine-4-carboxylic acid ethyl ester (VI) with 1-bromobutane (VII) by means of K2CO3 in methanol,followed by reduction of the ester group with LiAlH4 in THF.
参考文献标题:SB-204070: 5-HT4 receptor antagonists and their potential therapeutic utility
文献作者:Gaster,L.M.; Sanger,G.J.
参考来源:Drugs Fut 1994,19(12),1109
产品链接: CAS No. 148702-58-3››