AR-C89855AA
Chemical Name: 3-[2-(4-Hydroxy-2-oxo-2,3-dihydrobenzothiazol-7-yl)ethylamino]-N-[2-[2-(4-methylphenyl)ethoxy]ethyl]propanesulfonamide
CAS No. 189012-09-7, 189011-90-3 (monohydrochloride)
项目整合开发状态: Phase I/II
项目研究机构: AstraZeneca (Originator)
合成路线:Condensation of 2-(4-methylphenyl)ethanol (I) with t-Bu-bromoacetate (II) in toluene in the presence of NaOH and tetrabutylammonium bromide (TBAB) provides ethoxyacetic acid derivative (III),which is converted into acetamide (V) by reaction with oxalyl chloride (IV) in toluene/DMF followed by treatment with NH4OH.Reduction of (V) by reaction with borane-tetrahydrofuran (BH3稵HF) in THF yields ethanamine (VI),which is then coupled to chlorosulfonyl derivative (VII) in CH2Cl2 in the presence of TEA to afford compound (VIII).Reduction of the ester group of (VIII) by treatment with diisobutylaluminium hydride (DIBAL) in toluene furnishes aldehyde (IX),which is finally subjected to a reductive amination with benzothiazol derivative (X) by means of NaCNBH3 in MeOH/HOAc.
📌 参考资料/链接：
参考文献标题:Benzothiazolone derivs.
文献作者:Bonnert,R.V.; Brown,R.C.; Cage,P.A.; Ince,F.; Pairaudeau,G.(AstraZeneca plc)
参考来源:JP 1999512422; US 5846989; WO 9710227
📄 详细内容
合成路线:Condensation of 2-(4-methylphenyl)ethanol (I) with t-Bu-bromoacetate (II) in toluene in the presence of NaOH and tetrabutylammonium bromide (TBAB) provides ethoxyacetic acid derivative (III),which is converted into acetamide (V) by reaction with oxalyl chloride (IV) in toluene/DMF followed by treatment with NH4OH.Reduction of (V) by reaction with borane-tetrahydrofuran (BH3稵HF) in THF yields ethanamine (VI),which is then coupled to chlorosulfonyl derivative (VII) in CH2Cl2 in the presence of TEA to afford compound (VIII).Reduction of the ester group of (VIII) by treatment with diisobutylaluminium hydride (DIBAL) in toluene furnishes aldehyde (IX),which is finally subjected to a reductive amination with benzothiazol derivative (X) by means of NaCNBH3 in MeOH/HOAc.
参考文献标题:The discovery of dual D2-receptor and beta2-adrenoceptor agonists for the treatment of airway diseases
文献作者:Bonnert,R.; et al.
参考来源:16th Int Symp Med Chem (Sept 18 2000,Bologna) 2000,Poster PC161
产品链接: CAS No. 189012-09-7››