唑来膦酸的合成

咪唑和氯乙酸乙酯通过非均相反应合成咪唑乙酸乙酯，酸性水解得到咪唑乙酸盐酸盐，和三氯化磷、磷酸反应后再水解制得唑来膦酸。原料价廉易得，操作简便，反应总收率36％。     

室温离子液体1-丁基-3-甲基咪唑四氟硼酸盐的制备及其在有机合成中的应用

目的采用无溶剂微波法制备室温离子液体1丁基3甲基咪唑四氟硼酸盐,并以其作反应溶剂和催化剂合成乙酸苄酯。方法在家用微波炉中间歇式加热。结果与结论在家用微波炉中采用无溶剂、间歇加热方式制备得到1丁基3甲基咪唑四氟硼酸盐,该法反应时间短、收率高;通过引入室温离子液体作为溶剂和催化剂,实现了由醋酸钠与氯苄在相对温和条件下及较短的反应时间内微波法合成了乙酸苄酯,并获得较高收率。     

苯并咪唑-2-磺酸和2-氯苯并咪唑的大量制备

（取代）２－巯基苯并咪唑用过碳酸钠水溶液作氧化剂，制备（取代）苯并咪唑－２－磺酸，３例收率６５％～９２％。如继与在ＰＯＣｌ３中的ＰＣｌ５反应，即得高收率的（取代）２－氯苯并咪唑，３例收率８０％～８４％。苯并咪唑-2-磺酸和2-氯苯并咪唑的大量制备@丁健     

咪唑乙酸盐酸盐的制备

咪唑乙酸盐酸盐(1)是合成治疗恶性高钙血症药物唑来膦酸(zoledronic acid)的中间体[1].其合成可先以氨基乙缩醛为原料合成中间体SCNCH2CH(OEt)2,然后与乙基甘氨酸反应,产物经酸性水解及氧化反应即可制得咪唑乙酸,总收率42%[2],最后通入氯化氢气体,即得终产物1.此法步骤较多,操作繁琐.     

氯诺昔康的合成

以2，5－二氯噻吩为原料，经氯磺化、甲胺化、N－烷基化、环合、氨基取代等反应合成氯诺昔康。甲胺化时，以30％甲胺水溶液代替气体甲胺，简化了操作；N－烷基化时以相转移催化剂／氯乙酸甲酯代替钠氢／碘乙酸甲酯，提高了收率；环合反应更换溶剂系统使收率可达77％。工艺操作简便、安全，条件温和，成本低，总收率可由0．45％提高至12．3％。     

曲司氯铵的合成

二苯基羟乙酸与1,1'-羰基二咪唑反应生成二苯基羟乙酰咪唑,再与莨菪醇成酯、脱甲基、环合成季铵盐,制得毒蕈碱受体拮抗剂曲司氯铵,总收率约19%.     

羟甲香豆素合成工艺改进

本文介绍以１、４－二氧六环为溶剂,使间苯二酚与乙酰乙酸 较高的温度下反应生成羟甲香豆素,收率达７８％。     

唑来膦酸的合成与三废处理

目的：合成唑来膦酸并进行三废处理。方法：采用咪唑与氯乙酸乙酯反应,再用酸水解,得到咪唑乙酸,然后制备唑来膦酸。少量碱性和酸性废水先相互中和,然后用少量酸或碱中和,最后采用生物暴气法处理,废渣因量较少,采用深井焚烧法处理。结果：本工艺总收率为10．4％（以咪唑为起始原料计算）,三废较少,易于处理。结论：该合成路线所用原料国内均有大规模生产,成本较低、反应步骤短、反应条件温和、去掉了剧毒的氰化物、极大地减少了环境污染,适合工业化生产。     

抗肿瘤药物苹果酸舒尼替尼的合成

目的 合成抗肿瘤药物苹果酸舒尼替尼。方法 以乙酰乙酸叔丁酯为起始原料，通过Knorr吡咯合成法、脱叔丁氧羰基、Vilsmeier甲酰化、酯水解反应得中间体5-甲酰基-2,4-二甲基-1H-吡咯-3-羧酸（6），6与碳酰二咪唑反应生成酰基咪唑，不经分离直接用“一锅煮”方法与5-氟吲哚啉-2-酮和2-(二乙氨基)乙二胺缩合，最后成盐得到苹果酸舒尼替尼。 结果与结论 合成的苹果酸舒尼替尼经核磁共振、质谱和元素分析确证结构，总收率达28%。     

3-吡啶乙酸盐酸盐的合成

以烟酸乙酯为原料，经还原、氯代、氰化、水解等反应合成了骨吸收抑制剂利塞膦酸钠中间体3－吡啶乙酸盐酸盐。原料易得，反应条件温和，操作方便，总收率28．4％。     

唑来膦酸的合成工艺研究

目的 双膦酸药物唑来膦酸的合成工艺研究。方法 以咪唑和氯乙酸叔丁酯为原料,经咪唑N-烷基化、水解、缩合、重结晶等多步反应制备唑来膦酸。 结果 以32%的总收率实现了唑来膦酸的制备。结论 新工艺避免了剧毒品应用的同时,简化了操作步骤,具有原料易得、反应条件温和、操作简便等特点,有较好的工业化实施基础。     

Synthesis of a tripeptide with a C-terminal nitrile moiety and the inhibition of proteinases

The synthesis of the tripeptide d -Phe-Pro-Arg with the nitrite group instead of the carboxylgroup is described. Initially, the corresponding peptide amide was synthesized by conventional methods in solution using Boc and Fmoc as the protecting group for d -Phe. The dehydration in order to create the nitrite moiety was achieved by treating the peptide amide with phosphorus oxichloride or trifluoroacetic anhydride. Best results were obtained by the use of phosphorus oxichloride in pyridine as the solvent in the presence of imidazole. After deprotection of the N-terminal amino acid the crude product was purified by chromatography on Butyl-Fractogel® HW-40 (S). The purity of the final product was checked on a RP18 phase by hplc. The existence of the nitrite group was demonstrated by i.r. and ¹³C-n.m.r. spectra. The peptide nitrite exhibited a strong inhibition of thrombin compared to the tripeptide amide.     

2-(1-咪唑基)乙酸的新法合成

唑来膦酸 ( zoledronic acid)可用于治疗由肿瘤引起的高血钙症和恶性骨转移瘤。自 2 0 0 1年在日本和欧洲获准上市后 ,现已在全球 40多个国家上市。近期临床试验结果表明本品还具有良好的抗骨质疏松作用。2 - ( 1 -咪唑基 )乙酸 ( 1 )是制备唑来膦酸的关键中间体 ,其合成已有多     

氟喹酮的合成

目的合成氟喹酮并改进工艺。方法以2-氨基-5-硝基苯甲酸为起始原料,经缩合、还原、上保护基、环合、卤素交换、脱保护基,共七步反应制得氟喹酮。结果和结论改进后的方法避免了有毒有机溶剂的使用,在进行卤素交换反应时,用聚乙二醇作催化剂、无水二甲基甲酰胺代替乙二醇可以减少副产物,收率也有所提高。产物经1HNMR,IR,MS确证了结构。     

放射病预防药物的研究——Ⅲ.若干1,2-二硫戊烷叔胺类化合物的合成

1,2-二硫戊烷叔胺类化合物Ⅷ的合成途径如下:溴丙烯经Prins反应得4-溴代次甲基-1,3-二氧六环己烷Ⅹ,再与仲胺缩合得相应的取代叔胺二氧六环己烷Ⅺ,后者经水解得2,4-丁二醇胺Ⅻ。将Ⅺ或Ⅻ与硫脲及氢碘酸长时间反应,水解后用碘氧化,即得产物Ⅷ。其中化合物Ⅷ_a和ⅩⅣ_e对小白鼠急性电离辐射损伤有弱防护效果。     

Microwave-assisted linear approach toward highly substituted benzo[d]oxazol-5-yl-1H-benzo[d]imidazole on ionic liquid support

A novel and efficient diversity-oriented synthetic approach was employed to access the benzo[d]oxazol-5-yl-1H-benzo[d]imidazole on ionic liquid support, which helps to absorb microwave irradiation. In this paper, we successfully coupled 4-hydroxy-3-nitrobenzoic acid onto ionic liquid-immobilized o-phenylenediamine, which subsequently underwent an acid mediated, ring closure reaction leading to benzimidazole derivatives. After hydrogenation of the nitro group to an amine, the resulting ionic liquid conjugate was reacted with 1,1-thiocarbonyldiimidazols to yield an ionic liquid tagged-benzoxazol. Final skeletal diversity of the present scaffold was further achieved by S-alkylation with alkyl and aryl bromides. The benzo[d]oxazol-5-yl-1H-benzo[d]imidazole was finally cleaved smoothly from the ionic liquid support with sodium methoxide in methanol under microwave irradiation. This methodology has provided access to a small, diverse library by straightforward and simple operations and could be applied readily in various drug discovery programs.     

Spectrophotometric determination of ampicillin sodium in the presence of its degradation and polymerization products

A spectrophotometric method is described for the quantitative determination of ampicillin sodium [sodium salt of 6-(d (–)-phenylacetamido) penicillanic acid]. The method involves acetylation of ampicillin with acetic anhydride in aqueous solution at pH 9 to yield α-acetamido benzylpenicillin and subsequent measurement at 325 nm of α-acetamidobenzylpenicillenic acid mercuric mercaptide, formed in a quantitative yield on heating for 30 min at 60° in a 1·0m imidazole and 8 times 10^?4m mercuric chloride solution at pH 6·8. It has been demonstrated that degradation products do not interfere in the method whereas those di- and polymerization products of ampicillin which contain an intact β-lactam ring are capable of reacting with imidazole with the formation of penicillenic acid. A technique involving acid-catalysed opening of the β-lactam ring of these products under conditions where ampicillin is degraded to only a minor extent has been developed, and besides permitting a selective determination of ampicillin the technique permits the determination of the polymeric substances.