2-氨基-3-溴-6-氯吡啶的合成工艺研究
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摘要
标题化合物是一种重要的精细化工及医药中间体,可用于制备神经原纤维缠结显像剂、IRAK-4抑制剂及治疗退行性和炎症性疾病的化合物。对标题化合物的合成工艺路线进行了改进,以2-氨基-6-氯吡啶为起始原料,经氨基保护、溴代、脱保护基3步反应得到标题化合物,总收率为65. 13%。其结构经~1HNMR和MS确证。改进后的工艺具有原料成本低且商业可得、实验条件温和易控、操作及纯化过程简单、标题化合物纯度及收率较高的优点,可满足工业化生产需求。
The title compound is an important intermediate in fine chemicals and pharmaceuticals that can be used to prepare neurofibrillary tangles imaging agents,IRAK-4 inhibitors and compounds for the treatment of degenerative and inflammatory diseases.The synthesis route of the title compound was improved.2-Amino-6-chloropyridine was used as the starting material,and the title compound was synthesized by three steps of amino-protection,bromination and deprotection.The total yield was 65. 13%.The title compound was confirmed by~1HNMR and MS.The improved process has the advantages of low cost and commercially easy availability of raw materials,mild and easily controlled experiment conditions,simple operation and purification process,high purity and high yield of target products.It can meet industrial production demand.
The title compound is an important intermediate in fine chemicals and pharmaceuticals that can be used to prepare neurofibrillary tangles imaging agents,IRAK-4 inhibitors and compounds for the treatment of degenerative and inflammatory diseases.The synthesis route of the title compound was improved.2-Amino-6-chloropyridine was used as the starting material,and the title compound was synthesized by three steps of amino-protection,bromination and deprotection.The total yield was 65. 13%.The title compound was confirmed by~1HNMR and MS.The improved process has the advantages of low cost and commercially easy availability of raw materials,mild and easily controlled experiment conditions,simple operation and purification process,high purity and high yield of target products.It can meet industrial production demand.
引文
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[13]WIDDOWSON K L. Tricyclic nitrogen containing compounds for treating neisseria gonorrhoea infection:WO2 016 027 249[P].2016-02-25.
[14]LEE J H,LEE D H,HEO J O,et al.Preparation of organometallic compounds for organic light-emitting device:KR 2 018 020 878[P].2018-02-28.
[2]徐静.吡啶类化合物在医药领域的应用[J].中外医疗,2011,30(2):144-144.
[3]赵春深,李廷涛,周志旭,等.2-碘-3-溴-5-氯吡啶的合成[J].化学试剂,2017,39(9):1 021-1 022.
[4]ZHANG W,XU J,SUN Z Q,et al.Synthesis and application of halogenated pyridine compounds[J]. Fine Chem.Intermed.,2006,36(4):1-6.
[5]FENG C,BAO W J,WU Y G,et al.Synthesis and application of several halogenated pyridine compounds used as intermediate of pesticides[J]. Agrochemicals,2007,46(12):793-799.
[6]BLASS B.Pyrrolo[2,3-c]pyridines as imaging agents for neurofibrilary tangles[J]. ACS Med. Chem. Lett.,2016,7(5):444-446.
[7]RAO G V,SUSANTA S,SUBHENDU M,et al.Substituted azabicyclic compounds as IRAK-4 inhibitors and their preparation:WO 2 017 009 806[P].2017-01-19.
[8]RAO G V,SUSANTA S.Bicyclic heterocyclyl derivatives as IRAK4 inhibitors and their preparation:WO 2 015 104688[P].2015-07-16.
[9]ANDREW B,JOHN E P,WOLFGANG S,et al.Preparation of triazolopyridine compounds useful for the treatment of degenerative and inflammatory diseases:WO 2 008 065198[P].2008-06-05.
[10]SUNG C J,EIICHIRO I,MAKOTO K,et al.Preparation of diazaacenaphthylenecarboxamides and agents for increasing low-density lipoprotein receptor:JP 2 002 201193[P].2002-07-16.
[11]FENG Y B,CHEN Y T,HAMPTON S,et al. Bicyclic heteroaryls as kinase inhibitors and their preparation:WO 2 011 050 245[P].2011-04-28.
[12]TUMER J A. Regiospecific electrophilic substitution of aminopyridines:ortho lithiation of 2-,3-,and 4-(pivaloylamino)pyridines[J]. J. Org. Chem.,1983,48(20):3 401-3 408.
[13]WIDDOWSON K L. Tricyclic nitrogen containing compounds for treating neisseria gonorrhoea infection:WO2 016 027 249[P].2016-02-25.
[14]LEE J H,LEE D H,HEO J O,et al.Preparation of organometallic compounds for organic light-emitting device:KR 2 018 020 878[P].2018-02-28.