合成路线:The reaction of 5-carboxy-2-acetylthiophene (I) first with SOCl2 in refluxing toluene,and then with aqueous ammonia gives 5-carbamoyl-2-acetylthiophene (II),which is brominated with Br2 in hot acetic acid yielding 5-carbamoyl-2-bromoacetylthiophene (III).The cyclization of (III) with ammonium dithiocarbamate (A) in refluxing methanol-DMF affords 2-mercapto-4-(5'-carbamoyl-2'-thienyl)thiazole (IV),which is finally condensed with 1-chloro-3-tert-butylaminoisopropanol (V) by means of NaOH in water methanol.
合成路线:Ursodeoxycholic acid (I) was activated as the mixed anhydride (II) with ethyl chloroformate and triethylamine,and subsequently coupled with the triethylamine salt of taurine (III) to produce the title conjugated bile acid.Optionally,the mixed anhydride (II) was previously converted to the active phenol ester (V) by treatment with p-hydroxypropiophenone (IV),and subsequently condensed with taurine (III).Alternatively,ursodeoxycholic acid (I) was directly coupled to taurine (III) employing as the coupling reagents 2-isobutyl-N-isobutyloxycarbonyl-1,2-dihydroquinoline (IIDQ),diethylphosphorocyanidate (DEPC),or 2-ethoxy-N-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ) under microwave irradiation.
参考文献标题:Process for preparing ursodeoxycholic acid derivates and their inorganic and organic salts having therapeutic activity
文献作者:Reiner,A.(SkyePharma AG)
参考来源:EP 0272462
合成路线:The reaction of 5-carboxy-2-acetylthiophene (I) first with SOCl2 in refluxing toluene,and then with aqueous ammonia gives 5-carbamoyl-2-acetylthiophene (II),which is brominated with Br2 in hot acetic acid yielding 5-carbamoyl-2-bromoacetylthiophene (III).The cyclization of (III) with ammonium dithiocarbamate (A) in refluxing methanol-DMF affords 2-mercapto-4-(5'-carbamoyl-2'-thienyl)thiazole (IV),which is finally condensed with 1-chloro-3-tert-butylaminoisopropanol (V) by means of NaOH in water methanol.
参考文献标题:
文献作者:Hibino,T.; et al.
参考来源:JP 7525562
合成路线:The reaction of 5-carboxy-2-acetylthiophene (I) first with SOCl2 in refluxing toluene,and then with aqueous ammonia gives 5-carbamoyl-2-acetylthiophene (II),which is brominated with Br2 in hot acetic acid yielding 5-carbamoyl-2-bromoacetylthiophene (III).The cyclization of (III) with ammonium dithiocarbamate (A) in refluxing methanol-DMF affords 2-mercapto-4-(5'-carbamoyl-2'-thienyl)thiazole (IV),which is finally condensed with 1-chloro-3-tert-butylaminoisopropanol (V) by means of NaOH in water methanol.
参考文献标题:
文献作者:Hibino,T.; et al.
参考来源:JP 7576069
合成路线:The reaction of 5-carboxy-2-acetylthiophene (I) first with SOCl2 in refluxing toluene,and then with aqueous ammonia gives 5-carbamoyl-2-acetylthiophene (II),which is brominated with Br2 in hot acetic acid yielding 5-carbamoyl-2-bromoacetylthiophene (III).The cyclization of (III) with ammonium dithiocarbamate (A) in refluxing methanol-DMF affords 2-mercapto-4-(5'-carbamoyl-2'-thienyl)thiazole (IV),which is finally condensed with 1-chloro-3-tert-butylaminoisopropanol (V) by means of NaOH in water methanol.
参考文献标题:Synthesis and beta-adrenergic blocking action of a new thiazolylthiopropanolamine derivative
文献作者:Hara,Y.; et al.
参考来源:J Pharm Sci 1978,671334-35
产品链接: CAS No. 68377-92-4››