对氨基苯乙胺合成新工艺研究
摘要
对氨基苯乙胺是合成治疗膀胱过度活动症米拉贝隆的重要中间体。以硝基苯基乙腈作为起始材料,在催化剂钯碳的作用下,与水合肼反应,硝基还原得到对氨基苯乙腈,然后在雷尼镍的催化作用下,再次与水合肼反应,还原腈基得到对氨基苯乙胺,总收率达到89%。产品经过核磁氢谱和核磁碳谱表征。该路线反应操作简单,产品纯度好产量高,成本低,适合工业化大生产。
引文
[1]Wielage R C,Perk S,Campbell N L,et al.The cos effectiveness of mirabegron for the treatment of overactive bladder:three US perspectives[J].Journal of The American Geriatrics Society,2015,63:67.
[2]Matsuo T,Miyata Y,Kakoki K,et al.The efficacy of mirabegron additional therapy for lower urinary tract symptoms after treatment withα1-adrenergic receptor blocker monotherapy:prospective analysis of elderly men[J].Bmc Urology,2016,16(1):45-53.
[3]范文进,曾正英,吴之波,等.米拉贝隆合成工艺改进[J].精细化工中间体,2016,46(4):42-47.
[4]Bhide A A,Digesu G A,Fernando R,et al.Use of mirabegron in treating overactive bladder[J].International Urogynecology Journal,2012,23(10):1345-1348.
[5]Takasu T,Ukai M,Sato S,et al.Effect of(R)-2-(2-aminothiazol-4-yl)-4'-{2-[(2-hydroxy-2-phenylethyl)amino]ethyl}acetanilide(YM178),a novel selective beta3-adrenoceptor agonist,on bladder function[J].The Journal of Pharmacology&Experimental Therapeutics,2007,321(2):642-647.
[6]Takusagawa S,Lier J J V,Suzuki K,et al.Absorption,metabolism and excretion of[(14)C]mirabegron(YM178),a potent and selectiveβ(3)-adrenoceptor agonist,after oral administration to healthy male volunteers[J].Drug Metabolism&Disposition,2012,40(4):815-824.
[7]Chapple C R,Nitti V W,Khullar V,et al.Onset of action of theβ3-adrenoceptor agonist,mirabegron,in Phase II and IIIclinical trials in patients with overactive bladder[J].World Journal of Urology,2014,32(6):1565-1572.
[8]毛龙飞,苑李双,穆开蕊,等.米拉贝隆的合成研究[J].化学研究与应用,2016,28(4):521-524.
[9]Takusagawa S,Ushigome F,Nemoto H,et al.Intestinal absorption mechanism of mirabegron,a potent and selectiveβ3-adrenoceptor agonist:involvement of human efflux and/or influx transport systems[J].Molecular Pharmaceutics,2013,10(5):1783-1794.
[2]Matsuo T,Miyata Y,Kakoki K,et al.The efficacy of mirabegron additional therapy for lower urinary tract symptoms after treatment withα1-adrenergic receptor blocker monotherapy:prospective analysis of elderly men[J].Bmc Urology,2016,16(1):45-53.
[3]范文进,曾正英,吴之波,等.米拉贝隆合成工艺改进[J].精细化工中间体,2016,46(4):42-47.
[4]Bhide A A,Digesu G A,Fernando R,et al.Use of mirabegron in treating overactive bladder[J].International Urogynecology Journal,2012,23(10):1345-1348.
[5]Takasu T,Ukai M,Sato S,et al.Effect of(R)-2-(2-aminothiazol-4-yl)-4'-{2-[(2-hydroxy-2-phenylethyl)amino]ethyl}acetanilide(YM178),a novel selective beta3-adrenoceptor agonist,on bladder function[J].The Journal of Pharmacology&Experimental Therapeutics,2007,321(2):642-647.
[6]Takusagawa S,Lier J J V,Suzuki K,et al.Absorption,metabolism and excretion of[(14)C]mirabegron(YM178),a potent and selectiveβ(3)-adrenoceptor agonist,after oral administration to healthy male volunteers[J].Drug Metabolism&Disposition,2012,40(4):815-824.
[7]Chapple C R,Nitti V W,Khullar V,et al.Onset of action of theβ3-adrenoceptor agonist,mirabegron,in Phase II and IIIclinical trials in patients with overactive bladder[J].World Journal of Urology,2014,32(6):1565-1572.
[8]毛龙飞,苑李双,穆开蕊,等.米拉贝隆的合成研究[J].化学研究与应用,2016,28(4):521-524.
[9]Takusagawa S,Ushigome F,Nemoto H,et al.Intestinal absorption mechanism of mirabegron,a potent and selectiveβ3-adrenoceptor agonist:involvement of human efflux and/or influx transport systems[J].Molecular Pharmaceutics,2013,10(5):1783-1794.