[1]张义军,刘义稳,李德江.骨髓增殖性肿瘤治疗药物TG101348的合成工艺研究[J].江西师范大学学报(自然科学版),2014,(06):635-638.
　ZHANG Yi-jun,LIU Yi-wen,LI De-jiang.The Study on a Process of the Synthesis Bone Marrow Hyperplastic Tumortreatment Medicine TG101348[J].Journal of Jiangxi Normal University:Natural Science Edition,2014,(06):635-638.
点击复制

骨髓增殖性肿瘤治疗药物TG101348的合成工艺研究()
分享到：

《江西师范大学学报》（自然科学版）[ISSN:1006-6977/CN:61-1281/TN]

卷:
期数:
2014年06期
页码:
635-638
栏目:
出版日期:
2014-12-31

文章信息/Info

Title:
The Study on a Process of the Synthesis Bone Marrow Hyperplastic Tumortreatment Medicine TG101348
作者:
张义军;刘义稳;李德江
三峡大学生物与制药学院,湖北 宜昌,443002；三峡大学材料与化工学院,湖北 宜昌,443002
Author(s):
ZHANG Yi-jun；LIU Yi-wen；LI De-jiang
关键词:
TG101348; 合成; 工艺研究
Keywords:
TG101348; synthesis; technical study
分类号:
TQ463.53
文献标志码:
A
摘要:
研究了骨髓增殖性肿瘤治疗药物TG101348的合成工艺.将2，4-二羟基-5-甲基嘧啶与三氯氧磷、氨水发生氯化、取代反应生成2-氯-4-氨基-5-甲基嘧啶（Ⅲ），而后Ⅲ与N-叔丁基-3-溴苯磺酰胺（Ⅰ）发生Buchwald偶联反应得到3-[（2-氯-5-甲基-4-嘧啶基）胺基]-N-（叔丁基）苯磺酰胺（Ⅳ），Ⅳ再与CH3 OH-HCl反应得到3-[（2-氯-5-甲基-4-嘧啶基）胺基]-N-（叔丁基）苯磺酰胺盐酸盐（Ⅴ），最后Ⅴ与1-（4-氨基苯氧乙基）吡咯烷（Ⅵ）发生亲核取代反应得到TG101348，HPLC测得TG101348的纯度为99.7；.
Abstract:
The synthetic technique of TG101348 for treating bone marrow hyperplastic tumor was studied. 2-chloro-4-amino-5-methyl-pyrimidine(Ⅲ)was prepared by chlorination and substitution reaction of 2 ,4-dihydroxy-5-meth-ylpyrimidinnel,phosphorus oxychloride and ammonium hydroxide.Ⅲreacted with 3-bromo-N-t-butyl benzenesulfon-ic amide(Ⅰ) to give 3-[( 2-chloro-5-methyl-4-pyrimidinyl ) amino ]-N-t-butyl benzenesulfonic amide(Ⅳ) by Buchwald coupling reaction.Ⅳ reacted with CH3 OH-HCl to afford 3-[(2-chloro-5-methyl-4-pyrimidinyl)amino]-N-tert-butyl benzenesuiphon amide hydrochloride(Ⅴ). TG101348 was synthesized by nucleophilic substitution re-action of the intermediate Ⅴ and Ⅵ. HPLC purity is 99 . 7；.

参考文献/References:

[1] Tefferi A.JAK inhibitors for myeloproliferative neoplasms:clarifying facts from myths [J].Blood,2012,119(12):2721-2730.
[2] Anand S,Stedham F,Gudqin E,et al.Increased basal intracellular signaling patterns do not correlate with JAK2 genotype in human myeloproliferative neoplasms [J].Blood,2011,118(6):1610-1621.
[3] Well-Knecht K J,Ott G R,Cheng M,et al.2,7-Disubstituted-pyrrolotriazine kinase inhibitors with an unusually high degree of reactive metabolite formation [J].Chem Res Toxicol,2011,24(11):1994-2003.
[4] Ramakrishnan V,Kimlinger T,Haug J,et al.TG101209,a novel JAK2 inhibitor,has significant in vitro activity in multiple myeloma and displays preferential cytotoxicity for CD451 myeloma cells [J].American Journal of Hematology,2010,85(9):675-686.
[5] Wang Y,Fiskus W,Chong D G,et al.Cotreatment with panobinostat and JAK2 inhibitor TG101209 attenuates JAK2V617F levels and signaling and exerts synergistic cytotoxic effects against human myeloproliferative neoplastic cells [J].Blood,2009,114:5024-5033.
[6] Pardanan A,Hood J,Lasho T,et al.TG101209,a small molecule JAK2-selective kinase inhibitor potently inhibits myeloproliferative disorder-associated JAK2V617F and MPLW515L/K mutations [J].Leukemia,2007,21(8):1658-1668.
[7]李永双,李德江.双-三唑并
[3,4-b]-[ 1,3,4]噻二唑类化合物的合成及抗癌活性研究 [J].江西师范大学学报:自然科学版,2012,36(3):297-300.
[8] 张冰玉,金润铭.JAK2V617F突变及JAK2激酶抑制剂对骨髓增殖性肿瘤的影响 [J].临床血液学杂志,2014,27(9):817-820.
[9]秦伟,梁爱斌,傅建非.JAK2及其抑制剂与骨髓增殖性肿瘤的研究进展 [J].临床血液学杂志,2010,23(11):698-701.
[10] 谢叶香,李金恒,尹笃林.胺作为配体在钯催化偶联反应中的应用 [J].有机化学,2006,26(8):1155-1163.
[11] 张亮,吴劼.金属催化下芳基磺酸酯偶联反应的研究进展 [J].有机化学,2006,26(3):299-309.
[12] Cao Jianguo,Hood J,Sou R,et al.Bi-aryl meta-pyrimidine inhibtors of kinases [P].WO:2007/053452 A1,2007-05-10.

相似文献/References:

[1]李永双,李德江.双-三唑并[3,4-b]-[1,3,4]噻二唑类化合物的合成及抗癌活性研究[J].江西师范大学学报(自然科学版),2012,(03):297.
　LI Yong-shuang,LI De-jiang.The Synthesis and Anticancer Activities for Bis-Triazolo [3,4-b]-[1,3,4] Thiadiazole Derivatives[J].Journal of Jiangxi Normal University:Natural Science Edition,2012,(06):297.
[2]赵三虎,康锦,康晶燕,等.一个新颖结构四核咪唑盐的合成及表征[J].江西师范大学学报(自然科学版),2012,(03):304.
　ZHAO San-hu,KANG Jin,KANG Jing-yan,et al.The Synthesis and Characterization for a Novel Structure Imidazolium Salt with Four Nuclear[J].Journal of Jiangxi Normal University:Natural Science Edition,2012,(06):304.
[3]尹彦冰,许钱,尹官武.不同结构的α-羰基二硫缩烯酮化合物的合成及表征[J].江西师范大学学报(自然科学版),2012,(04):412.
　YIN Yan-bing,XU Qian,YIN Guan-wu.The Synthesis and Characterization of Some ?-Oxo Ketene-S, S-Acetals with Different Structures[J].Journal of Jiangxi Normal University:Natural Science Edition,2012,(06):412.
[4]崔汉峰,袁金斌,王星,等.异丁基硼酸的超声辐射合成[J].江西师范大学学报(自然科学版),2012,(04):415.
　CUI Han-feng,YUAN Jin-bin,WANG Xing,et al.The Ultrasound Irradiation Synthesis of Isobutylbornic Acid[J].Journal of Jiangxi Normal University:Natural Science Edition,2012,(06):415.
[5]肖伟,肖转泉,聂旭亮,等.莰烯酸酰胺的合成及其晶体结构[J].江西师范大学学报(自然科学版),2012,(05):527.
　XIAO Wei,XIAO Zhuan-quan,NIE Xu-liang,et al.The Synthesis and Crystal Structure for a New Camphene Acid Amide[J].Journal of Jiangxi Normal University:Natural Science Edition,2012,(06):527.
[6]高明,李德江.甲氧头孢中间体7-MAC的合成工艺改进[J].江西师范大学学报(自然科学版),2012,(06):551.
　GAO Ming,LI De-jiang.The Process Improvement in the Synthetic Method of Intermediate of Methoxy Cephalosporin 7-MAC[J].Journal of Jiangxi Normal University:Natural Science Edition,2012,(06):551.
[7]叶红德,童怀多,邹如意,等.氘代二茂铁炔酮的合成及其在机理研究中的应用[J].江西师范大学学报(自然科学版),2012,(06):558.
　YE Hong-de,TONG Huai-duo,ZOU Ru-yi,et al.The Synthesis of Deuterated Ferrocenyl Alkynone and Its Application in Mechanism Research[J].Journal of Jiangxi Normal University:Natural Science Edition,2012,(06):558.
[8]贾晓丽,王强,宫晓瑞,等.含咔唑结构单元新型席夫碱的合成[J].江西师范大学学报(自然科学版),2012,(06):562.
　JIA Xiao-li,WANG Qiang,GONG Xiao-rui,et al.The Synthesis of Novel Schiff Base Containing Carbazole Moiety[J].Journal of Jiangxi Normal University:Natural Science Edition,2012,(06):562.
[9]张克松,王艳玲,陈义兴,等.2-芳基-3-(3-氟苯甲酰胺基)-4-噻唑啉酮类化合物的合成及抗癌活性研究[J].江西师范大学学报(自然科学版),2013,(02):148.
　ZHANG Ke-song,WANG Yan-ling,CHEN Yi-xing,et al.Synthesis and Antibacterial Activity of 2-Aryl-3-(3-Fluorobenzoylamino)-4-Thiazolidinone[J].Journal of Jiangxi Normal University:Natural Science Edition,2013,(06):148.
[10]喻理德,崔汉峰,王星,等.受体酪氨酸激酶抑制剂Dovitinib的合成[J].江西师范大学学报(自然科学版),2013,(02):152.
　YU Li-de,CUI Han-feng,WANG Xing,et al.The Synthesis of Tyosine Kinase Inhibitor Dovitinib[J].Journal of Jiangxi Normal University:Natural Science Edition,2013,(06):152.

备注/Memo

备注/Memo:
国家自然科学基金(31100080)；湖北省自然科学基金(2011CDB186)
更新日期/Last Update: 1900-01-01