CAS: 1492952-76-7; (R)-N-(4-(Chlorodifluoromethoxy)Phenyl)-6-(3-Hydroxypyrrolidin-1-yl)-5-(1H-Pyrazol-3-yl)Nicotinamide

上下游产品

(R)-5-Bromo-N-(4-(Chlorodifluoromethoxy)Phenyl)-6-(3-Hydroxypyrrolidin-1-yl)Nicotinamide

3-Bromo-2-Chloro-5-Pyridinecarbonyl Chloride置于potassium Phosphate,四(三苯基膦)钯,N,N-二异丙基乙胺,三氟乙酸体系中,用 四氢呋喃,二氯甲烷,异丙醇,甲苯 用作溶剂,化学反应 11.0H,反应生成变构bcr-Abl抑制剂(asciminib)
参考文献:发现ascminib(abl001),Bcr-Abl1酪氨酸激酶活性的变构抑制剂
标题:发现ascminib(abl001),Bcr-Abl1酪氨酸激酶活性的变构抑制剂
摘要:慢性粒细胞性白血病(cml)源自bcr-Abl1癌蛋白的组成型活性.靶向atp结合位点的酪氨酸激酶抑制剂(tkis)已将cml转化为慢性可控制的疾病.但是,由于atp位点突变阻碍了药物结合,一些患者出现了耐药性.我们描述了asciminib(abl001)的发现,这是第一种到达临床的变构bcr-Abl1抑制剂.Asciminib结合bcr-Abl1的肉豆蔻口袋,并保持抗tki耐药性atp站点突变的活性.尽管由于肉豆蔻酸位点突变会产生抗药性,但这些突变对atp竞争性抑制剂敏感,因此,Asciminib与atp竞争性tki的组合可抑制抗药性的出现.使用NMR和x射线的基于片段的筛选产生了肉豆蔻口袋的配体.基于NMR的构象分析指导了这些非活性配体向abl1抑制剂的转化.对效力,理化,药代动力学和类药物特性进行进一步的基于结构的优化,最终达到了asciminib的要求,目前正在对cml患者进行临床研究.
Doi:10.1021/acs.Jmedchem.8B01040

专利信息

专利号:US-5849936-A
优先权日:1995-03-15
标题:Method for the synthesis of bis-tetrahydrofuranyl annonaceous acetogenins
发明人：HOYE THOMAS R; TAN LUSHI
权利人:UNIVERISTY OF MINNESOTA
摘要:A method for the synthesis of bis-tetrahydrofranyl Annonaceous acetogenins, including the natural products and analogs thereof, is provided which proceeds by the Pd-mediated coupling of a bis-tetrahydrofuranyl-subunit comprising a terminal alkyne, with a (C4)-hydroxybutenolide subunit comprising a terminal vinyl iodide, followed by selective reduction of the resulting enyne.

专利号:US-2024199637-A1
优先权日:2021-04-21
标题 :Improved process for the preparation of 7-(morpholinyl)-2-(n-piperazinyl)methylthieno[2, 3-c]pyridine derivatives
发明人：KOMPELLA AMALA; VAGICHERLA KAMESWARA RAO; LANKI REDDY TIRUMALA REDDY; PESARU NARMADA; MUDDASANI PULLA REDDY; NANNAPANENI VENKAIAH CHOWDARY
权利人:NATCO PHARMA LTD
摘要:The present invention describes an improved second generation process for the synthesis of NRC-1111 (1,5-[2-[[4-(methylsulfonyl)-1-piperazinyl]methyl]-7-(4-morpholinyl)thieno[2,3-c] pyridine-5-yl]-2-pyrimidinamine) dimethane sulfonate and NRC-1109 (II, 5-[3-methyl-2-[(4-methylsulfonylpiperazin-1-yl)methyl]-7-morpholino-thieno[2,3-c]pyridin-5-yl]pyrimidin-2-amine) dimethane sulfonate. This process is cost effective, high yielding and industrially feasible process for the synthesis of compounds of formulae I and II with high purity. Formula (I) Formula (I): Râ•?H for NRC-1111 and Formula (II): Râ•?CH3 for NRC-1109 NRC-1111 and NRC-1109 are potential anti-cancer agents.

专利号:US-11884623-B2
优先权日:2022-05-23
标题:Process for the preparation of (R)-4-propyl pyrrolidine-2-one, a key intermediate for synthesis of brivaracetam
发明人：DIVI MURALI KRISHNA PRASAD; BOLNENI NAGESWARA RAO; BANDARUPALLI LEELA MAHESWARA RAO
权利人:DIVIS LABORATORIES LTD
摘要:A process for the preparation of (R)-4-propyl-pyrrolidine-2-one, is provided which includes enzymatic conversion of dimethyl 3-propyl pentanedioate selectively into (S)-3-(2-methoxy-2-oxoethyl) hexanoic acid using Novozyme's Promea® enzyme, amidation of (S)-3-(2-methoxy-2-oxoethyl) hexanoic acid, followed by ester hydrolysis to obtain (S)-3-(2-amino-2-oxoethyl) hexanoic acid having high chiral purity >99% and converting the amide to amine by Hofmann rearrangement and cyclization resulting in (R)-4-propyl-pyrrolidine-2-one. It is further converted to Brivaracetam by N-alkylation with 2-bromobutyric acid, esterification followed by enzymatic resolution.

专利号:US-2009281176-A1
优先权日:2007-11-01
标题:Process for the synthesis of ramelteon and its intermediates
发明人：KANSAL VINOD KUMAR; MISTRY DHIRENKUMAR N; VASOYA SANJAY L; PATEL RAKESH; JADAV ARPAN M
权利人:KANSAL VINOD KUMAR; MISTRY DHIRENKUMAR N; VASOYA SANJAY L; PATEL RAKESH; JADAV ARPAN M
摘要:A process for the preparation of ramelteon and intermediates useful in the process. The process suitable for industrial scale provides increased yield and/or greater purity with fewer process steps.

专利号:WO-2011148392-A1
优先权日:2010-05-28
标题 :Process for the preparation of (2s,4s,5s,7s)-n-(2-carbamyl-2- methylpropyl)-5-amino-4-hydroxy-2,7-diisopropyl-8-[4-methoxy-3-(3- methoxypropoxy)phenyl]-octanamide hemifumarate and its intermediates thereof
发明人：SATYANARAYANA REDDY MANNE; THIRUMALAI RAJAN SRINIVASAN; ESWARAIAH SAJJA; VENKAT REDDY GHOJALA; RAMA SUBBA REDDY KARAMALA; SAHADEVA REDDY MARAMREDDY
权利人:MSN LAB LTD; SATYANARAYANA REDDY MANNE; THIRUMALAI RAJAN SRINIVASAN; ESWARAIAH SAJJA; VENKAT REDDY GHOJALA; RAMA SUBBA REDDY KARAMALA; SAHADEVA REDDY MARAMREDDY
摘要:The present invention relates to a process for the preparation of (2S,4S,5S,7S)-N-(2- Carbamoyl-2-methylpropyl)-5-amino-4-hydroxy-2,7-diisopropyl-8-[4-methoxy-3-(3-methoxy propoxy )phenyl]-octanamide compound of formula- 1 and its pharmaceutically acceptable salts thereof. Further, relates to the processes for the preparation of (R)-4-(2-(halomethyl)-3- methylbutyl)-l-methoxy-2-(3-methoxypropoxy) benzene and (R)-2-(4-methoxy-3-(3-methoxy propoxy) benzyl)-3-methyIbutan-l-ol useful intermediates in the synthesis of compound of formula- 1.

专利号:WO-2011161690-A1
优先权日:2010-06-23
标题:Processes for the preparation of (+)-n,n-dimethyl-2-[1-(naphthalenyloxy) ethyl] benzene methanamine and intermediates thereof
发明人：MOHAN RAO DODDA; KRISHNA REDDY PINGILI; JITHENDER AADEPU; VENUGOPAL BINGI
权利人:SYMED LABS LTD; MOHAN RAO DODDA; KRISHNA REDDY PINGILI; JITHENDER AADEPU; VENUGOPAL BINGI
摘要:The present invention relates to processes for the preparation of S(+)-N,N-dimethyl-2-[1-(naphthalenyloxy)ethyl]benzene methanamine and intermediates thereof. More particularly the present invention relates to preparation of the compound 3(S)-(+)-N,N-dimethylamino-3-phenyl propanol useful as intermediate in the synthesis of pharmaceutically active compounds.