Novel hexahydrofuro[3,4-b]-2(1H)-pyridones from 4-aryl substituted 5-alkoxycarbonyl-6-methyl-3,4-dihydropyridones

The title compounds 6 have been prepared in a one-step procedure from the corresponding 4-aryl substituted 5-alkoxycarbonyl-6-methyl-3,4-dihydropyridones 4 in good yields. Quantum chemical calculations reveal a non-planar molecule with a distorted dihydropyridone ring and two favoured conformations. The 13C nmr data and theoretical calculations support a strong push-pull effect on the olefinic moiety.     

6-氨基-5-氰基-3-甲基-4-(3-硝基苯)-1-苯基吡唑[3,4-b]并吡啶与人血清白蛋白结合作用的光谱特征

采用紫外光谱法和荧光光谱法研究了6-氨基-5-氰基-3-甲基-4-(3-硝基苯)-1-苯基吡唑[3,4-b]并吡啶(6A)与人血清白蛋白(HSA)的结合作用,利用同步荧光法和三维荧光法研究了6A与HSA作用前后人血清白蛋白的构象变化。观测到生理pH7.4条件下6A使HSA的紫外吸收峰增强,特征荧光峰猝灭。Stern-Volmer曲线显示,6A对HSA的荧光猝灭可能是一个单一的静态猝灭过程,并且得出18℃和37℃时的结合位点数和结合常数。根据F rster非辐射转移理论可求出6A与HSA作用距离r=3.73 nm;根据基本热力学参数ΔH、ΔS和ΔG判断6A和HSA主要通过氢键和范德华力发生相互作用。     

6-Amino-5-cyano-1H,4H-pyrazolo[3,4-b]pyrans

The reaction of 3-methyl-1-phenyl-5-pyrazolene with arylideneamino nitriles in alcohol leads to the formation of 3-methyl-4(1-aryl-2,2-dicyanoethyl)-5-pyrazolones, which are readily cyclized in the presence of bases to the corresponding 6-amino-5-cyano-3-methyl-4-aryl- 1H,4H-pyrazolo[3,4-b]pyrans. The structures of the intermediate and final products were confirmed by the IR, UV, PMR, and mass spectra.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 801–806, June, 1982.     

Synthesis and properties of 5-acetyl-3-cyano-4-isobutyl-6-methyl-3,4-dihydropyridine-2(1H)-thione

Condensation of isovaleric aldehyde with cyanothioacetamide and acetylacetone or its enamine produces 5-acetyl-3-cyano-4-isobutyl-6-methyl-3,4-dihydropyridine-2(1H)-thione, from which 5-acetyl-3-cyano-4-isobutyl-6-methylpyridine-2(1H)-thione and the corresponding substituted 2-alkylthio-1,4-dihydropyridines are prepared. T. G. Shevchenko Lugansk State Pedagogical Institute, Lugansk 348011, Ukraine; e-mail: kgb@lgpi.lugansk.ua; N. D. Zelinskii Institute of Organic Chemistry of the Russian Academy of Sciences, Moscow 117913, Russia; Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 516–519, April, 1999.     

Synthesis and Crystal Structure of 4-（4-Chlorophenyl）-6-methyl-5-methoxy-caronyl-3,4-dihydropyrimidin-2（H）-one

1 INTRODUCTION Biginelli reaction is a three-component condensa-tion of ethyl acetoacetate, benzaldehyde and urea forthe synthesis of 3,4-dihydropyrimidin-2(1H)-ones(Scheme 1). The reaction can be carried out in aone-pot fashion in alcohol solution in t…     

Synthesis of 5-Amino-4-imino-3,4-dihydropyrido[3,4-d]pyridazin-1(2H)-one Derivatives

Russian Journal of Organic Chemistry -     

Synthesis of 3-cyano-5-ethoxycarbonyl-4-isobutyl-6-methyl-3,4-dihydropyridine-2(1H)-thione by three-component condensation

Condensation of isovaleraldehyde with cyanothioacetamide and ethyl acetoacetate (or its enamine) gives 3-cyano-5-ethoxycarbonyl-4-isobutyl-6-methyl-3,4-dihydropyridine-2(1H)-thione. This compound was used in the synthesis of substituted 1,4-dihydropyridin-2-yl sulfides. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 166–168, January, 1999.     

3-甲基-5-氰基-6-氨基-1-苯基-4-(3,4-二甲氧基苯基)-1,4-二氢吡喃[2,3-c]吡唑的合成和晶体结构

标题化合物C22H20N4O3 3是由2-氰基-3-(3,4-二甲氧基苯基)丙烯腈1和3-甲基-1-苯基-2-吡唑-5-酮2在KF-Al2O3催化下在N,N-二甲基甲酰胺(DMF)溶剂中反应而得。结构通过单晶X-射线衍射分析确定,其晶体属于三斜晶系,空间群Pī,a = 9.450(3),b = 10.876(2), c = 11.435(2) ,a = 115.51(1), b = 102.82(1),g = 98.47(2), Mr = 388.42, V = 994.1(3) 3,Dc = 1.298 g/cm3, Z = 2, m (MoKa) = 0.089 mm-1, F(000) = 408。晶体结构用直接法解出,使用全矩阵最小二乘法对原子参数进行修正,最后的偏离因子R = 0.0420,wR = 0.1070。单晶X-射线衍射分析表明平面Ⅰ与平面Ⅱ、平面Ⅲ、平面Ⅳ的夹角分别为102.31、29.24和1.43。平面Ⅱ与平面Ⅲ和平面Ⅳ的夹角分别为73.50和100.91,平面Ⅲ和平面Ⅳ的夹角为27.81, 另外晶体中还存在分子间氢键。     

Reactivity of 4-azido- and 4-amino-6-methyl-2H-pyran-2-one. Preparation of 1-(6-methyl-2-oxopyran-4-yl)-1,2,3-triazoles and 5-oxopyrano[4,3-b]pyridines

1,3-Dipolar cycloadditions of stable 4-azido-6-methyl-2H-pyran-2-one 1 with electron-rich alkenes and alkynes lead to 4,5-substituted 1-(6-methyl-2-oxopyran-4-yl)-1,2,3-triazoles. Iminophosphoranes derived from 1 have also been synthesized. 5-Oxopyrano[4,3-b]pyridines are prepared by reaction of 4-amino-6-methyl-2H-pyran-2-one 2 with β-dicarbonyl compounds.     

Syntheses of 6-Amino-1-(β-D-ribofuranosyl)-1H-pyrazolo[3,4-d]-1,3-oxazin-4-one,an isostere of oxanosine,and the guanosine analog 6-amino-1-(β-d-ribofuranosyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one via ring closure of pyrazole-5-thioureido intermediates

6-Amino-1-(β-D-ribofuranosyl)-1H-pyrazolo[3,4-d]-1,3-oxazin-4-one ( 4 ), an isostere of the nucleoside antibiotic oxanosine has been synthesized from ethyl 5-amino-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)pyrazole-4-carboxylate ( 6 ). Treatment of 6 with ethoxycarbonyl isothiocyanate in acetone gave the 5-thioureido derivative 7 , which on methylation with methyl iodide afforded ethyl 1-(2,3-O-isopropylidene-β-D-ribofuranosyl)-5-[(N'-ethoxycarbonyl-S-methylisothiocarbamoyl)amino]pyrazole-4-carboxylate ( 8 ). Ring closure of 8 under alkaline media furnished 6-amino-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)-1H-pyrazolo[3,4-d]-1,3-oxazin-4-one ( 10 ), which on deisopropylidenation afforded 4 in good yield. 6-Amino-1-(β-D-ribofuranosyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one ( 5 ) has also been synthesized from the AICA riboside congener 5-amino-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)pyrazole-4-carboxamide ( 12 ). Treatment of 12 with benzoyl isothiocyanate, and subsequent methylation of the reaction product with methyl iodide gave 1-(2,3-O-isopropylidene-β-D-ribofuranosyl)-5-[(N'-benzoyl-S-methylisothiocarbamoyl)amino]pyrazole-4-carboxamide ( 15 ). Base mediated cyclization of 15 gave 6-amino-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one ( 14 ). Deisopropylidenation of 14 with aqueous trifluoroacetic acid afforded 5 in good yield. Compound 4 was devoid of any significant antiviral or antitumor activity in culture.