1-[二-(4-氟苯)甲基]-4-酰基取代哌嗪类衍生物的合成

1-[二-(4-氟苯)甲基]-4-取代哌嗪是一类重要的药物中间体,随着哌嗪环4-位引入不同的取代基可以产生不同的生物活性,如治疗偏头痛药物氟桂利嗪、洛美利嗪,抗氧化剂、钙拮抗剂、癌症治疗中多种抗药性的调节剂(modulator of MDR)等;此外,含有酰基结构单元的哌嗪     

2-[3-(4-甲氧基苯氧基)丙基]-1,3-二乙酰硫基丙烷的合成

自组装单层膜(SAMs)技术是自20世纪80年代以来快速发展起来的一个新型有机成膜技术,它是通过表面活性剂的头基与基底之间产生化学吸附,在界面上自发形成的有序的单分子层[1].     

3-氧代-3-[3-三氟甲基-5,6-二氢[1,2,4]三唑并[4,3-α]吡嗪-7(8H)-基]-1-苯基丙烷-1-胺的合成

三唑类衍生物是重要的化工和药物合成中间体,而稠合三唑类衍生物因其独特的生理活性更是得到了广泛关注[1-2],其中3-三氟甲基-5,6,7,8-四氢[1,2,4]三唑并[4,3-α]哌嗪与β-氨基酸缩合得到的化合物是一类重要的二肽基肽酶-Ⅳ抑制剂 [3-4],可作为2型糖尿病的治疗药物,如2006年经美国FDA批准在美国上市的西他列汀(sitagliptin),此外二肽基肽酶-Ⅳ抑制剂还可用于肥胖症和高血压等疾病的预防和治疗[5].     

(E)-2-[2-(6-氯嘧啶-4-基氧基)苯基]-3-甲氧基丙烯酸甲酯的合成工艺改进

以3-(α-甲氧基)亚甲基苯并呋喃-2-(3H)-酮为原料,经3步反应合成了杀菌剂嘧菌酯的重要中间体——(E)-2-[2-(6-氯嘧啶-4-基氧基)苯基]-3-甲氧基丙烯酸甲酯(4),总收率61%。4的结构经NMR表征。     

1-[4-(二甲氨基)苯亚甲基氨基]-4-苯基硫脲的合成及手性晶体结构

对二甲氨基苯甲醛和苯基氨基硫脲缩合反应生成对二甲氨基苯甲醛缩氨基苯硫脲{1-[4-(dimethylamino)ben- zylidene]-4-phenylthiosemicarbazide}, 并从溶液中析出手性晶体. 元素分析、红外光谱、紫外光谱、核磁谱、质谱和X射线衍射测定其组成和结构. 晶体属正交晶系, P2₁2₁2₁空间群, a＝0.77038(14) nm, b＝1.1428(2) nm, c＝1.6726(3) nm, V＝1.4726(5) nm³, Z＝4, D_c＝1.346 g/cm³, F(000)＝632, μ＝0.219 mm^－1, 可观测点精修最终偏离因子: R＝0.0407, wR＝0.1157. 化合物的晶体结构和固态圆二色谱表明化合物在结晶过程中发生单一对映体的手性堆积.     

可见光诱导的2-(苄基氨基)苯甲酰胺合成4(3H)-喹唑啉酮

发展了一种环境友好的可见光诱导的反应.该方法在简单、温和的反应条件下可以通过2-(苄基氨基)苯甲酰胺来高效合成4(3H)-喹唑啉酮化合物.不使用任何金属、光催化剂和其他添加剂,仅在室温下用blue LED照射,反应就可以顺利进行并高收率得到相应的喹唑啉酮化合物.该反应具有反应底物范围广、官能团兼容性好、操作简单等优点,...     

4-甲氧基-3-[3-(吗啉-4-基)丙氧基]苯甲腈的合成研究

以3-羟基-4-甲氧基苯甲醛为原料,在甲酸、甲酸钠、盐酸羟胺作用下,将醛基转化为氰基,在含有碳酸钾的DMF中,所得化合物与N-(3-氯丙基)吗啉反应得目标化合物,总收率为87.5%。产物结构由1HNMR表征。本方法具有操作简单、易于纯化、收率高等特点,为工业化生产提供实验基础。     

4-氯-6-甲氧基-7-(N-甲基-4-哌啶甲氧基)喹唑啉的合成

凡德他尼(vandetanib)是由阿斯利康公司研发的口服小分子多靶点酪酸激酶抑制剂,可同时作用于肿瘤细胞EGFR、VEGFR和RET酪氨酸激酶[1,2],2006年1月获欧洲罕见病药品委员会(COMP)批准推荐,用于治疗髓甲状腺癌、乳腺癌、骨髓瘤等[3].     

4,6-二甲氧基-2-[甲氧脲基硫代脲基]嘧啶的合成、晶体结构和理论计算

利用2-氨基-4,6-二甲氧基嘧啶在干燥条件下与硫氰酸钾、氯甲酸甲酯在乙酸乙酯溶液中反应制得4-(4,6-二甲氧基嘧啶-2-基)-3-硫代脲酸甲酯, 在二甲基甲酰胺溶液中培养出单晶, 通过X射线单晶结构分析法测定分子结构和晶体结构, 晶体属单斜晶系, 空间群为C2/m, 晶胞参数为: a＝1.6672(3) nm, b＝0.66383(12) nm, c＝1.1617(2) nm, β＝109.275(2)°, V＝1.2136(4) nm³, D_c＝1.490 g/cm³, μ＝0.281 mm^－1, F(000)＝568, Z＝4, R₁＝0.0341, wR₂＝0.1042. 运用Gaussian 03程序, 在6-311G的基组水平上, 用HF, MP2以及B3LYP三种计算方法对标题化合物进行了几何全优化, 并对其成键情况及自然键轨道(NBO)进行了分析.     

微波辐射下2-[4-二-(4-氟苯)甲基]哌嗪乙酰腙化合物的合成

微波辐射条件下, 以丙酮作溶剂, 1-[二-(4-氟苯)甲基]哌嗪与氯乙酸乙酯反应得到2-[二-(4-氟苯)甲基]哌嗪乙酸乙酯(1), 1与水合肼在微波辐射条件下反应得到2-[二-(4-氟苯)甲基]哌嗪乙酰肼(2), 进一步在微波辐射条件下由2-[二- (4-氟苯)甲基]哌嗪乙酰肼(2)与取代芳香醛反应制得目标化合物3a～3f. 合成的6个目标化合物通过熔点测定和质谱、红外光谱、核磁共振氢谱分析、元素分析对其结构进行确证.     

Synthesis of 1-R-2-amino-3-[2-(benz)azolyl]-4(5H)-ketopyrroles

A study has been made of the interaction of 2-[2-(benz)azolyl]3-keto-4-chlorobutanenitriles with primary aliphatic amines. This is a convenient method for the synthesis of 2-amino-3-[2-(benz)azolyl]-4(5H)-ketopyrroles.Tarasa Shevchenko Kiev University, Kiev 252601, Ukraine; e-mail dov@fosfor.kiev.ua. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 50–57, January, 1998.     

Synthesis and Crystal Structure of 1-（4-Chlorophenyl）-2-cyano-3-amino-3a-hydroxy-3a,3b ,6, 7-te trah y drobenzo[ 4,5]indene

1 INTRODUCTION dimerization of α,β-unsaturated ketones[10]. Herein we discuss the crystal structure of the title compound In the early seventies three groups of investiga- synthesized by the reaction of 2-cyano-3-(4-chloro- tors[1~3] have established that low-valent titanium phenyl)-3-(1-tetralon-2-yl) induced by TiCl4/Zn system. can abstract oxygen from ketones or aldehydes, lead- When 2-cyano-3-(4-chlorophenyl)-3-(1-tetra- lon-2-yl) ing to the formation of olefins. A variety of other…     

Synthesis of 4-[3-(1H)-indolyl]-2-[N-guanidinomethyl]thiazole dihydrochloride

The title compound 3b was synthesized in three steps from acetaminothioacetamide ( 4b ) in 15% overall yield. This represents the first synthesis of a 2-guanidinomethylthiazole, which is a homolog of an important pharmacophore, 2-guanidinothiazole.     

Synthesis of 3-(L-Threo-Glycerol-l-YL)-6,7-Dimethyl-Pyrazolo[3,4-b]Quinoxalines

Abstract

Reaction of dehydro-L-ascorbic acid with 1,2-diamino-4,5-dimethylbenzene and arylhydrazines afforded 3-[l-(aryl)hydrazono-L-threo-2,3,4-trihydroxybutyl]-6,7-dimethyl-lH-quinoxalin-2-ones. Their dehydrative cyclization gave 1-aryl-3-(L-threo-glycerol-1-yl)-6,7-dimethylpyrazolo[3,4-b] quinoxalines, whose acetylation and periodate oxidation were studied.     

Synthesis and Reactions of 1-(3-Chloropropyl)-6,7-dimethoxy-3-methylbenzo[c]pyrylium Perchlorate

Acid-catalyzed acylation of 3,4-dimethoxyphenylacetone with -chlorobutyryl chloride gave 1-(3-chloropropyl)-6,7-dimethoxy-3-methylbenzo[c]pyrylium perchlorate. Recyclization of the product with nitrogen nucleophiles (ammonia, primary amines, hydrazine derivatives, hydroxylamine) led through the corresponding isoquinolinium salts to benzo[f]indolizinium, pyridazino[2,1-b]isoquinolinium, and 1,2-oxazino[2,1-b]isoquinolinium salts.     

Synthesis of (2S,3S)-[3-(2)H1]-4-methyleneglutamic acid and (2S,3R)-[2,3-(2)H2]-4-methyleneglutamic acid

(2S,3S)-[3-(2)H1]-4-Methyleneglutamic acid 1a and (2S,3R)-[2,3-(2)H2]-4-methyleneglutamic acid 1b have been synthesised for use in biosynthetic and metabolic studies.     

Synthesis, molecular and crystal structure of 2-[2-(2-amino-3-cyano-4H-chromen-4-yl)-cyclohexylidene]malononitrile

Condensation of salicylaldehyde with cyclohexylidenemalononitrile and hydrazine hydrate results in 2-[2-(2-amino-3-cyano-4H-chromen-4-yl)cyclohexylidene]malononitrile, the structure of which was studied by XRD.     

Synthesis of 3-amino-4-(thienyl-2)furazan

3-Amino-4-(thienyl-2)furazan (3) has been synthesized from 2-acetylthiophene (4) by several routes. Nitrosation of 4, followed by oximation of the resulting oxime salt 5, gave a 6:1 mixture of the E,E and E,Z isomers of thienylglyoxime (1). Estimation of differences and analogies of these isomers' reactivity have been carried out. Oxidation and dehydration of 1 gave furoxan 11 and furazan 2, respectively. Conversion of 2, 12, 13, and 11a, b into the target amine 3 by base-promoted reaction with hydroxylamine has been reported. © 1997 John Wiley & Sons, Inc.     

Synthesis of [4-amino-5-(R-benzyl)-1,3-thiazol-2-ylsulfanyl] acetic acids

Russian Journal of Organic Chemistry - (4-Amino-1,3-thiazol-2-ylsulfanyl)acetic acids were synthesized by reaction of α-thiocyanatonitriles with sulfanylacetic acid in boiling acetonitrile.