抗肿瘤药布格替尼的合成

以2-碘苯胺为起始原料,经“一锅法”反应制得{2-[（2,5-二氯嘧啶-4-基）氨基]苯基}二甲基氧化膦（3）; 1-甲基-4-（哌啶-4基）哌嗪（4）与5-氟-2-硝基苯甲醚反应后,经氢化还原得2-甲氧基-4-[4-（4-甲基哌嗪-1-基）哌啶-1-基]-苯胺（6）; 3和6反应合成了布格替尼,总收率48.5%,纯度99.6%,其结构经¹H NMR和MS（ESI）确证。     

3-氧代-4-（2,4,5-三氟苯基）丁腈的合成

以2,4,5-三氟苯乙酸为起始原料,经氯化和酰化反应得2-氰基-3-羟基-4-（2,4,5-三氟苯基）丁-2-烯酸乙酯（2）; 2经水解脱羧合成了3-氧代-4-（2,4,5-三氟苯基）丁腈,总收率61.5%,纯度97.6%,其结构经¹H NMR和MS（ESI）确证。     

简便的"一锅法"合成氟代芳烃

本文采用改进的Schiemann反应, 合成了一些用Schiemann反应不易制得的氟代芳烃。本方法中, 芳烃氟硼酸重氮盐水溶液可不经分离, 室温下"一锅法"反应, 简便合成了对氟硝基苯、对氟苯乙酮, 氟代苯甲酸等, 分离产率为25-62%。     

N-{3-氯4-[(3-氟苄基)氧基]苯基}-6-碘喹唑啉-4-胺的合成工艺改进

以2-胺基-5-碘苯甲酸为起始原料,经四步反应合成了新型喹唑啉类抗肿瘤药物拉帕替尼的关键中间体-N-{3-氯4-[(3-氟苄基)氧基]苯基}-6-碘喹唑啉-4-胺,总收率77.9%,其结构经1H NMR和ESI-MS确证.Williamson醚化反应的最佳条件为:4-(6-碘喹唑啉-4-基氨基)-2-氯苯酚(5)30.0 mmol,K2CO3 24.8 g,18-冠-6 0.79 g,KI 0.49 g,丙酮250 mL.于35℃反应12 h,收率90.1%.     

不对称催化合成2-[[3-{[3-氯-5-(三氟甲基)吡啶-2-基]-氧基}苯氧基](苯基)甲基]丙烯酸甲酯

以苯甲醛、丙烯酸甲酯、2,3-二氯-5-三氟甲基吡啶和间苯二酚为原料,分别合成了MBH乙酸酯（6）和取代苯酚（9）;在(DHQD)₂PHAL催化下,6和9经不对称反应立体选择性合成了2-【【3-{[3-氯-5-(三氟甲基)吡啶-2-基]-氧基}苯氧基】(苯基)甲基】丙烯酸甲酯,产率50%, ee 94%,其结构经¹H NMR, ¹³C NMR和HR-MS确证。     

咪唑类酸性离子液体在Beckmann重排中的应用

以N-甲基咪唑和1,4-丁烷磺内酯反应制得1-甲基-3-磺酸丁基咪唑内盐（MBsIm）; MBsIm分别与H₂SO₄、 CF₃SO₃H和CF₃COOH反应合成了3种咪唑类酸性离子液体：1-甲基-3-磺酸丁基咪唑三氟甲烷磺酸盐（[MBsIm][OTf]）、 1-甲基-3-磺酸丁基咪唑硫酸氢盐（[MBsIm][HSO₄]）和1-甲基-3-磺酸丁基咪唑三氟乙酸盐（[MBsIm][CF₃COO]）,其结构经¹H NMR和¹³C NMR确证。并考察了其在液相Beckmann重排反应中的催化作用。结果表明：[MBsIm][OTf]Z-nCl₂体系的选择性和收率达99％以上,重复使用3次后,转化率维持在90%以上。     

2-甲氧基-3-氟-4-碘吡啶的合成

2-甲氧基-3-氟-4-碘吡啶是一个重要的医药化工中间体,其合成路线未见文献报道。以2-甲氧基-3-氟-5-氯吡啶为起始原料,经氢解和碘代两步反应合成标题化合物,总收率62.8%,其结构经¹H NMR, ¹³C NMR和MS确证。     

高纯度(98.5%)夫沙那韦-d_4的合成

以硝基苯-d5为原料,经还原、保护、磺酰化、脱保护、氧化和亲核取代反应制得中间体——对硝基苯磺酰氯-d4(7)。以(2R,3S)-N-叔丁氧羰基-3-氨基-1,2-环氧-4-苯基丁烷为原料,经开环反应制得(1S,2R)-N-[1-苯甲基-2-羟基-3-(异丁胺基)丙基]氨甲酸叔丁酯(9);9与7经磺化反应合成(2R,3S)-N-[(3-氨基-2-羟基-4-苯基)丁基]-N-异丁基-4-硝基苯磺酰胺盐酸盐-d4(10);10依次经酰化、磷酰化、加氢还原和醋酸钙成盐反应合成了夫沙那韦-d4,总收率33%,纯度98.5%,其结构经1H NMR和EI-MS确证。     

1-[2′,4′-二氟-(1,1′-联苯)-4-基苯基甲基]-咪唑的合成

以2,4-二氟联苯为起始原料,经酰化反应制得2′,4′-二氟-(1,1′-联苯)-4-基苯基甲酮(2);2经NaBH4还原得2′,4′-二氟-(1,1′-联苯)-4-基苯基甲醇(3);3经氯代得2′,4′-二氟-(1,1′-联苯)-4-基苯基氯甲烷(4);4与咪唑发生亲核取代反应合成了1-[2′,4′-二氟-(1,1′-联苯)-4-基苯基甲基]-咪唑(5). 2～5为新化合物,其结构经1H NMR, IR, MS和元素分析确证.     

光引发剂(4-甲苯基)(4-异T基苯基)碘鎓六氟磷酸盐的合成研究

以对甲苯胺为原料,经重氮化、KI分解得到对-碘甲苯.在NH4Cl存在下,对-碘甲苯在过硫酸铵的氧化下与异丁苯反应,得到(4-甲苯基)(4-异丁基苯基)碘鎓氯.在丙酮溶剂中,(4-甲苯基)(4-异丁基苯基)碘鎓氯与六氟磷酸钾进行离子交换,得到目的产物(4-甲苯基)(4-异丁基苯基)碘鎓六氟磷酸盐.总收率为46.7%.通过...     

Investigation of nitrogen- and sulfur-containing heterocycles

The corresponding N-(3-pyridyl)hydroxamic acid derivatives were obtained by reductive desulfuration of [2-(ethoxycarbonylmethylthio)-6-chloro-3-pyridyl]hydroxamic acid amide, benzylamide, and morpholide. The amides were synthesized by reaction of [2-(ethoxycarbonylmethylthio)-6-chloro-3-pyridyl]hydroxamic acid ester with diethylaminoethylamine and pyrrolidine. Heating of the ester and morpholide of [2-(ethoxycarbonylmethylthio)-6-chloro-3-pyridyl]hydroxamic acid with H₂SO₄ gives 2-chloropyrido[2,3-b] [1,4]thiazin-6-one.See [1] for communication XXVI.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 676–678, May, 1973.     

Experimental and theoretical studies on the functionalization reactions of 4-benzoyl-1,5-diphenyl-1H-pyrazole-3-carboxylic acid and acid chloride with 2,3-diaminopyridine

The 1H-pyrazole-3-carboxylic acid 2 was converted in good yield (69%) into the corresponding 1H-pyrazole-3-carboxamide 5 via reaction of the acid chloride 3 with 2,3- diaminopyridine (4). A different product, the 3H-imidazo[4,5-b] pyridine derivative 6, was formed from the reaction of 3 with 4 and base in benzene for 5 hours. The structures of the synthesized compounds were determined spectroscopically. The mechanism of the reaction between 3 and 4 was examined theoretically.     

新型Br(o)nsted-Lewis酸性离子液体的合成及其在松香二聚反应中的应用

合成、表征了新型Bronsted-Lewis酸性离子液体1-(3-磺酸)-丙基-3-甲基咪唑氯锌酸盐([HO3S-(CH2)3-mim]Cl-ZnCl2),并将其用于催化松香二聚反应.结果表明,[HO3S-(CH2)3-mim]Cl-ZnCl2(ZnCl2摩尔分数x＞0.5)为Bronsted和Lewis双酸性,且以[HO3S-(CH2)3-mim]Cl-ZnCl2 (x=0.64)的催化性能较佳.在松香5.0 g,甲苯15 g,离子液体质量分数5%,反应温度110℃和反应时间4 h的较佳实验条件下,所得产物聚合松香的软化点为118 ℃.此外,该催化剂的使用有利于产物的分离且分离的离子液体催化剂具有良好的重复使用性能.     

4-甲基-7，10-二氢苯并[h]香豆素的合成研究

以1-萘酚(6)为起始原料，经过Birch还原得到5，8-二氢-1-萘酚(7)；7与乙酰 乙酸乙酯在不同条件下缩合合成了4-甲基-7，10-二氢苯并[h]香豆素(4)．研究结 果表明，无氧和酸催化的反应条件对缩合反应是至关重要的．在没有酸催化的条件 下，反应生成3-乙酰基-2-羟基-6-甲基-吡喃-4-酮(8)，并通过单晶X射线衍射分析 确定了产物的结构；在酸催化的条件下，除了生成产物4外，还伴随生成脱氢芳构 化产物4-甲基苯并[h]香豆素(5)，而且在不同条件下二者的比例不同，其中以甲磺 酸为催化剂、在氮气保护下并加入抗氧化剂无水Na_2SO_3为最佳反应条件，化学选 择性约为70：30(4：5)，收率49．1％．     

新型含1,2,3-三氮唑的染料木素糖缀合物的合成

以染料木素为起始原料,经两步反应制得中间体7-O-炔丙基染料木素(3);以CuI为催化剂,3与叠氮乙酰基糖经Click反应合成了7-O-［1-(2,3,4,6-四-O-乙酰基-β-D-糖苷)1H-1,2,3-三氮唑-4-甲基］-染料木素(5a~5c); 5a~5c经去乙酰基制得三种含1,2,3-三氮唑的氮苷染料木素糖缀合物(6a~6c)。3, 5和6均为新化合物,其结构经¹H NMR, ¹³C NMR和HR-MS表征。     

The metalla-Pinner reaction between Pt(IV)-bound nitriles and alkylated oxamic and oximic forms of hydroxamic acids

The nitrile ligands in the platinum(IV) complexes trans-[PtCl4(RCN)2] (R=Me, Et, CH2Ph) and cis/trans-[PtCl4(MeCN)(Me2SO)] are involved in a metalla-Pinner reaction with N-methylbenzohydroxamic acid (N-alkylated form of hydroxamic acid, hydroxamic form; F1), PhC(=O)N(Me)OH, to achieve the imino species [PtCl4[NH=C(R)ON(Me)C(=O)Ph]2 (1-3) and [PtCl4[NH=C(Me)ON(Me)C(=O)Ph](Me2SO)] (7), respectively. Treatment of trans-[PtCl4(RCN)2] (R=Me, Et) and cis/trans-[PtCl4(MeCN)(Me2SO)] with the O-alkylated form of a hydroxamic acid (hydroximic form), i.e. methyl 2,4,6-trimethylbenzohydroximate, 2,4,6-(Me3C6H2)C(OMe)=NOH (F2A), allows the isolation of [PtCl4[NH=C(R)ON=C(OMe)(2,4,6-Me3C6H2)]2] (5, 6) and [PtCl4[NH=C(Me)ON=C(OMe)(2,4,6-Me3C6H2)](Me2SO)] (8), correspondingly. In accord with the latter reaction, the coupling of nitriles in trans-[PtCl4(EtCN)2] with methyl benzohydroximate, PhC(OMe)=NOH (F2B), gives [PtCl4[NH=C(Et)ON=C(OMe)Ph]2] (4). The addition proceeds faster with the hydroximic F2, rather than with the hydroxamic form F1. The complexes 1-8 were characterized by C, H, N elemental analyses, FAB+ mass-spectrometry, IR, 1H and 13C[1H] NMR spectroscopies. The X-ray structure determinations have been performed for both hydroxamic and hydroximic complexes, i.e. 2 and 6, indicating that the imino ligands are mutually trans and they are in the E-configuration.     

富马酸奈拉西坦的合成工艺改进

报道了一种合成富马酸奈拉西坦(7)的新工艺。以衣康酸二甲酯和苄胺为起始原料,经Michael加成和分子内环合反应制得1-苄基-5-氧代吡咯烷-3-羧酸甲酯(3); 3经NaBH₄还原得1-苄基-4-羟甲基-吡咯烷-2-酮(4); 4经甲磺酰化反应得1-苄基-5-氧代吡咯烷-3-羧酸甲磺酸酯(5); 5经氨解得奈拉西坦(6); 6与富马酸经成盐反应合成7,总收率78.4%,其结构经¹H NMR确证。     

水介质中9,10-二芳基吖啶的洁净合成

水介质中在十二烷基磺酸钠(SDS)催化下, 席夫碱与双甲酮反应合成了一系列9,10-二芳基吖啶衍生物, 同时分离得到一种中间产物. 所有产物的结构通过红外光谱和1H NMR光谱确定, 产物10-(4-氯苯基)-9-(4-甲氧基苯基)-3,3,6,6-四甲基-3,4,6,7,9,10-六氢化吖啶-1,8(2H,5H)-二酮(3i)和中间产物2-{4-氯苯基-[2-(4-甲氧基苯基氨基)-4,4-二甲基-6-氧代环已-1-烯基]甲基}-3-羟基-5,5-二甲基环已-2-烯酮(4h)的结构还通过单晶X射线衍射分析确证.     

Synthesis of analogs of 5(4)-aminoimidazole-4(5)-carboxamide

In order to obtain 5(4)-aminoimidazole-4(5)carboxamide antagonists, the.hydrazides of 5(4)-aminoimidazole-4(5)-carboxylic acid and 5(4)-aminoimidazole-4(5)hydroxamic acid were synthesized, and the reaction of 5(4)-bromo-4(5)sulfamoylimidazole with amines was studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1421–1422, October, 1971.     

Type 2 intramolecular N-acylnitroso diels-alder reaction: stereoselective synthesis of bridged bicyclic oxazinolactams

[reaction: see text] The type 2 intramolecular N-acylnitroso Diels-Alder reaction has been employed for the synthesis of substituted bridged bicyclic oxazinolactams. Upon oxidation of hydroxamic acid 6, a 3-benzylated oxazinolactam (7) was synthesized with complete diastereoselectivity. Elaboration of cycloadduct 7 liberated a cis-3,7-disubstituted azocin-2-one (9).