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,C15H10Cl2FNO2,326.1569,2-chloro-4-[(5-fluoro-2-methylbenzoy

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摘 要:,C15H10Cl2FNO2,326.1569,2-chloro-4-[(5-fluoro-2-methylbenzoyl)amino]benzoyl chloride
  • 【化学名】2-chloro-4-[(5-fluoro-2-methylbenzoyl)amino]benzoyl chloride
  • 【CAS登记号】
  • 【结构式】,C15H10Cl2FNO2,326.1569,2-chloro-4-[(5-fluoro-2-methylbenzoy--药物合成数据库
  • 【分子式】C15H10Cl2FNO2
  • 【分子量】326.1569
  • 【来源】
  • 【合成情况】 
  • 〖目标产物〗Lixivaptan, WAY-VPA-985, VPA-985
  • 〖合成路线〗
  • 〖合成方法〗The acylation of 4-amino-2-chlorobenzoic acid methyl ester (VII) with 5-fluoro-2-methylbenzoyl chloride (VI) gives the corresponding amide (VIII), which is hydrolyzed at the ester group yielding the corresponding free acid (IX). The reaction of (IX) with SOCl2 affords the acyl chloride (X), which is finally condensed with the pyrrolobenzodiazepine (II) (obtained by the reductocyclization of 1-(2-nitrobenzyl)pyrrole-2-carbaldehyde (I)) to provide the target compound.
  • 〖参考〗Albright, J.D.; Delos Santos, E.G.; Reich, M.F.; et al.; 5-Fluoro-2-methyl-N-[4-(5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-ylcarbonyl)-3-chlorophenyl]benzamide (VPA-985): An orally active arginine vasopressin antagonist with selectivity for V2 receptorspan>【CAS登记号】/span>/li> >
  • 〖目标产物〗Lixivaptan, WAY-VPA-985, VPA-985
  • 〖合成路线〗
  • 〖合成方法〗The acylation of 4-amino-2-chlorobenzoic acid methyl ester (VII) with 5-fluoro-2-methylbenzoyl chloride (VI) gives the corresponding amide (VIII), which is hydrolyzed at the ester group yielding the corresponding free acid (IX). The reaction of (IX) with SOCl2 affords the acyl chloride (X), which is finally condensed with the pyrrolobenzodiazepine (II) (obtained by the reductocyclization of 1-(2-nitrobenzyl)pyrrole-2-carbaldehyde (I)) to provide the target compound.
  • 〖参考〗Albright, J.D.; Reich, M.F.; Sum, F.-W.; Delos Santos, E.G. (American Cyanamid Co.); Tricyclic diazepine vasopressin antagonists and oxytocin antagonists. CA 2128956; EP 0636625; JP 1995157486; US 5516774
  • 〖目标产物〗Lixivaptan, WAY-VPA-985, VPA-985
  • 〖合成路线〗
  • 〖合成方法〗The acylation of 4-amino-2-chlorobenzoic acid methyl ester (VII) with 5-fluoro-2-methylbenzoyl chloride (VI) gives the corresponding amide (VIII), which is hydrolyzed at the ester group yielding the corresponding free acid (IX). The reaction of (IX) with SOCl2 affords the acyl chloride (X), which is finally condensed with the pyrrolobenzodiazepine (II) (obtained by the reductocyclization of 1-(2-nitrobenzyl)pyrrole-2-carbaldehyde (I)) to provide the target compound.
  • 〖参考〗Reich, M.F.; Delos Santos, E.G.; Sum, F.-W.; Albright, J.D. (American Cyanamid Co.); Tricyclic diazepine vasopressin antagonists and oxytocin antagonists. US 5733905
  • 〖目标产物〗Lixivaptan, WAY-VPA-985, VPA-985
  • 〖合成路线〗
  • 〖合成方法〗The acylation of 4-amino-2-chlorobenzoic acid methyl ester (VII) with 5-fluoro-2-methylbenzoyl chloride (VI) gives the corresponding amide (VIII), which is hydrolyzed at the ester group yielding the corresponding free acid (IX). The reaction of (IX) with SOCl2 affords the acyl chloride (X), which is finally condensed with the pyrrolobenzodiazepine (II) (obtained by the reductocyclization of 1-(2-nitrobenzyl)pyrrole-2-carbaldehyde (I)) to provide the target compound.
  • 〖参考〗Albright, J.D.; Sum, F.-W.; Delos Santos, E.G.; Reich, M.F. (American Cyanamid Co.); Tricyclic diazepine vasopressin antagonists and oxytocin antagonists. US 5736540
  • 〖目标产物〗
  • 〖合成路线〗
  • 〖合成方法〗The condensation of 4,4-dimethyl-2-(2-thienyl)-4,5-dihydrooxazole (I) with 2-nitrobenzyl bromide (II) by means of first with BuLi and then with tributylstannyl chloride and Pd(PPh)3)4 in ethyl ether gives 4,4-dimethyl-2-[3-(2-nitrobenzyl)-2-thienyl]-4,5-dihydrooxazole (III), which is cyclized by means of HCl in refluxing acetone/water yielding 9,10-dihydro-4H-thieno[2,3-c][1]benzazepin-10-one (IV). The reduction of (IV) by means of LiAlH4 in refluxing THF affords 9,10-dihydro-4H-thieno[2,3-c][1]benzazepine (V), which is finally condensed with 2-chloro-4-(5-fluoro-2-methylbenzamido)benzoyl chloride (VI) by means of triethylamine in dichloromethane.
  • 〖参考〗Aranapakam, V.; Grosu, G.T.; Chan, P.S.; Ru, X.; Saunders, T.; Albreight, J.D.; Coupet, J.; Mazandarani, H.; 4,10-Dihydro-5H-thieno[3,2-c][1]benzazepine derivatives and 9,10-dihydro-4H-thieno[2,3-c][1]benzazepine derivatives as orally active arginine vasopan>【CAS登记号】/span>/li> > ??l耀?k See Full Image">img src='/f
  • 〖目标产物〗
  • 〖合成路线〗
  • 〖合成方法〗The condensation of 4,4-dimethyl-2-(2-thienyl)-4,5-dihydrooxazole (I) with 2-nitrobenzyl bromide (II) by means of first with BuLi and then with tributylstannyl chloride and Pd(PPh)3)4 in ethyl ether gives 4,4-dimethyl-2-[3-(2-nitrobenzyl)-2-thienyl]-4,5-dihydrooxazole (III), which is cyclized by means of HCl in refluxing acetone/water yielding 9,10-dihydro-4H-thieno[2,3-c][1]benzazepin-10-one (IV). The reduction of (IV) by means of LiAlH4 in refluxing THF affords 9,10-dihydro-4H-thieno[2,3-c][1]benzazepine (V), which is finally condensed with 2-chloro-4-(5-fluoro-2-methylbenzamido)benzoyl chloride (VI) by means of triethylamine in dichloromethane.
  • 〖参考〗Albright, J.D.; Reich, M.F.; Sum, F.-W. (American Cyanamid Co.); N-Acylated tricyclic azaheterorings useful as vasopressin antagonists. CA 2128955; EP 0640592; JP 1995179430; US 5512563; WO 9747624
  • 〖目标产物〗
  • 〖合成路线〗
  • 〖合成方法〗The condensation of 4,4-dimethyl-2-(2-thienyl)-4,5-dihydrooxazole (I) with 2-nitrobenzyl bromide (II) by means of first with BuLi and then with tributylstannyl chloride and Pd(PPh)3)4 in ethyl ether gives 4,4-dimethyl-2-[3-(2-nitrobenzyl)-2-thienyl]-4,5-dihydrooxazole (III), which is cyclized by means of HCl in refluxing acetone/water yielding 9,10-dihydro-4H-thieno[2,3-c][1]benzazepin-10-one (IV). The reduction of (IV) by means of LiAlH4 in refluxing THF affords 9,10-dihydro-4H-thieno[2,3-c][1]benzazepine (V), which is finally condensed with 2-chloro-4-(5-fluoro-2-methylbenzamido)benzoyl chloride (VI) by means of triethylamine in dichloromethane.
  • 〖参考〗Du, X.; Albright, J.D. (American Cyanamid Co.); Tricyclic benzazepine vasopressin antagonists. US 5736538
 
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