Synthesis of 1,3-Bis[3-X-2-(X-acetoxy)propyl]-6-methyl- 1,2,3,4-tetrahydropyrimidine-2,4-diones

A procedure was developed for synthesizing nitrogen-and-sulfur-containing pyrimidine derivatives by reactions of 1,3-bis(3-chloro-2-hydroxypropyl)-6-methyluracil with 1-butanethiol and chloroacetyl chloride, followed by treatment of the resulting 1,3-bis[3-chloro-2-(chloroacetoxy)propyl]-6-methyl-1,2,3,4-tetrahydropyrimidine-2,4-dione with 1-butanethiol, morpholine, and piperidine. Oxidation of the sulfur-containing products with NaIO₄ gave the corresponding sulfoxides.     

Synthesis of Macrocyclic Pyrimidine Derivatives

A reaction was studied of previously unknown 1,3-bis(2-hydroxy-3-chloropropyl)uracil, 1,3-bis(2- hydroxy-3-chloropropyl)-6-methyluracil, and 1,3-bis(2-hydroxy-3-chloropropyl)-5-fluorouracil with 1,3-bis[3-(3-methyl-2H-5-pyrazolon-1-yl)-2-hydroxypropyl]-6-methyluracil.     

Synthesis of 5-Alkyl-1,3-bis[2-hydroxy-3-(6-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-3-yl)propyl]-6-methyl-1,2,3,4-tetrahydropyrimidine-2,4-diones

6-Methyluracil sodium salt reacts with 1,3-bis(3-chloro-2-hydroxypropyl)-6-methyluracils in DMF, yielding products of alkylation at the nitrogen atom in position 3 of the uracil ring.     

Alkylation of Pyrimidine Derivatives with Chloroacetic Acid Esters

Alkylation of 6-methyluracil, 5-hydroxy-6-methyluracil, and 6-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-ylammonium sulfate with isopropyl and ethyl chloroacetates afforded previously unknown alkyl 2-(6-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetates, alkyl 2-(1-alkoxycarbonylmethyl-6-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-3-yl)acetates, 1,3-bis(alkoxycarbonylmethyl)-6-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-ylammonium sulfates, and alkyl 2-[1,3-bis(alkoxycarbonylmethyl)-6-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yloxy]acetates.     

Synthesis of 1,3-Bis[2-hydroxy-3-(3-methyl-5-oxo-2,5-dihydro-1-pyrazolyl)propyl)uracils

A reaction was studied of newly synthesized 1,3-bis(2-hydroxy-3-chloropropyl)uracil and 1,3-bis(2-hydroxy-3-chloropropyl)-6-methyluracil with hydrazine hydrate followed by treating the compounds formed with ethyl acetoacetate. The hydrazones obtained cyclized into pyrazolones in the presence of sodium methylate.     

Chemo-, regio-, and stereoselective cyclizations of 1,3-bis(trimethylsilyloxy)-1,3-butadienes with alpha-chloroacetic acid chlorides and alpha-chloroacetic acetals

Treatment of 1,3-bis(trimethylsilyloxy)-1,3-butadienes with alpha-chlorocarboxylic acid chlorides resulted in chemo- and regioselective formation of 6-chloro3,5-dioxo esters, which were regioselectively converted into functionalised 3(2H)furanones. Chemo- and regioselective condensation of 1,3-bis(trimethylsilyloxy)-1,3-butadienes with alpha-chloroacetic dimethyl acetal afforded 6-chloro-5-methoxy-3-oxo esters, which could be regio- and stereoselectively transformed into 2-alkylidene-4-methoxytetrahydrofurans.     

HIV-1 RT抑制剂研究I.1,3-二苄基-6-(3,4-环氧丁基)尿嘧啶的合成

报道了1,3-二苄基-6-(3,4-环氧丁基)尿嘧啶的合成新方法.以6-甲基尿嘧啶(1)为起始物,经1,3-二苄基-6-甲基尿嘧啶(2)及未见文献报道的1,3-二苄基-6-(3-丁烯基)尿嘧啶(3)和1,3-二苄基-6-(3-羟基-4-溴丁基)尿嘧啶(4),首次高收率合成了1,3-二苄基-6-(3,4-环氧丁基)尿嘧啶(5),并对其化学结构进行了表征.     

The synthesis of oxazolo- and oxazino[3,2-d] [1,4]benzodiazepinones

Cyclization of 2′-benzoyl-4′-chloro-2-[(2-hydroxypropyl)amino]acetanilide (8) and 2′-bcnzoyl-4-ehloro-2-[(3-hydroxypropyl)amino]acetanilide ( 7 ) led to the respective oxazolo (3) and oxazino (5) analogs of 7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one. Cyclization of 2′-benzoyl-4′-chloro-2-[2,3-dihydroxypropyl)amino]acetanilide ( 9 ) could produce either the oxazolo ( 4 ) or oxazino ( 10 ) analog. Data is presented to show that cyclization occurred to give the oxazolo (4) analog.     

Regioselective synthesis of 4-chlorophenols, 10-chloro-7-hydroxy-6H-benzo[c]chromen-6-ones, and 4-chloro-1-hydroxy-9H-fluoren-9-ones based on [3+3] cyclizations of 1,3-bis(silyloxy)-1,3-dienes with 2-chloro-3-silyloxy-2-en-1-ones

A variety of 4-chlorophenols, 10-chloro-7-hydroxy-6H-benzo[c]chromen-6-ones, and 4-chloro-1-hydroxy-9H-fluoren-9-ones were prepared by formal [3+3] cyclizations of 1,3-bis(silyloxy)-1,3-dienes with 2-chloro-3-(silyloxy)alk-2-en-1-ones.     

1-(3,4-二甲氧基）苯乙基-3-环氧丙基-5-氰基-6-甲基脲嘧啶的合成及晶体结构

标题化合物1-（3，4-二甲氧基）苯乙基-3-环氧丙基-5-氰基-6-甲基脲嘧啶是 由1-（3，4-二甲氧基）苯乙基-5-氰基-6-甲基脲嘧啶在NaOH水溶液中与环氧氯丙 烷反应制得。结构通过单晶X射线衍射分析确定，其晶体属于单斜晶系，空间群 P2_1/a, 晶胞参数：a = 1.09(10) nm, b = 1.43(10) nm, c = 1.20(8) nm, V = 1.868 nm~3，Z = 4, D_c = 1.32 Mg/m~3, F(000) = 784。并用波谱法对分离得 到的副产物进行了结构表征。     

Regioselective synthesis of benzo[c]chromen-6-ones by one-pot cyclocondensation of 1,3-bis(trimethylsilyloxy)-1,3-butadienes with 4-chloro-2-oxo-2H-chromene-3-carbaldehyde

The cyclocondensation of 4-chloro-2-oxo-2H-chromene-3-carbaldehyde with 1,3-bis(silyloxy)-1,3-butadienes provides a convenient synthesis of benzo[c]chromen-6-ones.     

Process development and large-scale synthesis of NK1 antagonist

A scaleable synthetic route is described to obtain 2-(4-acetylpiperadin-1-yl)-6-[3,5-bis(trifluoromethyl)phenylmethyl]-4-(2-methylphenyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,5]oxazocin-5-one (1, KRP-103) as a neurokinin (NK)(1) antagonist. The key step in the synthesis is the intramolecular cyclization of N-[3,5-bis(trifluoromethyl)phenylmethyl]-N-(3-hydroxypropyl)-4-chloro-6-(2-methylphenyl)-2-methylthiopyrimidine-5-carboxamide (15) which was obtained by amide formation between 4-(2-methylphenyl)-2-methylthio-6-oxo-1,6-dihydropyrimidine-5-carboxylic acid (8) and 3-[3,5-bis(trifluoromethyl)phenylmethylamino]-1-propanol (3). Treatment of 15 with 1,8-diazabicyclo[5,4,0]undec-7-ene provided 6-[3,5-bis(trifluoromethyl)phenylmethyl]-4-(2-methylphenyl)-2-methylthio-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,5]oxazocin-5-one (6). This intermediate (6) is transformed into the candidate compound (1) by two steps; oxidation, and substitution reaction of the resultant sulfone (7) with 1-acetylpiperazine. This synthetic method is free of chromatographic purification and is amenable to large scale synthesis.     

First Analog of Pyrimidine Nucleosides with Two D-Ribofuranose Residues

Russian Journal of Organic Chemistry - The reaction of 1,3-bis(pent-4-yn-1-yl)-6-methyluracil with 2,3,5-tri-O-acetyl-β-D-ribofuranosyl azide gave...     

Functional Acetal Methacrylates: III. Electrophilic Addition of Diols to 2-(Vinyloxy)ethyl Methacrylate

Reactions of 2-(vinyloxy)ethyl methacrylate with diols [ethylene glycol, diethylene glycol, triethylene glycol, oligoethylene glycol-400, Z-2-butene-1,4-diol, 2-butyne-1,4-diol, 1,1,3,3-tetramethyl-1,3-bis(3-hydroxypropyl)disiloxane, 2,2-bis(4-hydroxyphenyl)propane] and polyols (glycerol, pentaerythritol) under electrophilic conditions (1 wt% of CF₃COOH, 20-60°C, 1-3 h) result in quantitative formation of functional acetal methacrylates.     

Research on the pyrimidine series

The reaction of 4-chloro-2-ethylthio-6-methylpyrimidine with 30% H₂O₂ in ethanol with heating forms 5-chloro-6-methyluracil instead of the expected 4-chloro-2-hydroxy-6-methylpyrimidine. Under similar conditions but in the presence of HC1, 6-methyluracil and 2-ethylthio-4-hydroxy-6-methylpyrimidine are also converted into 5-chloro-6-methyluracil.For part IV, see [10].     

Synthesis of pyrimidinophanes containing nitrogen atoms in polymethylene bridges

The reactions of 1,3-bis(-bromobutyl- or -pentyl)-6-methyluracil with 1,3-bis(-ethylaminobutyl- or -pentyl)-6-methyluracil afforded pyrimidinophanes containing N atoms in bridging polymethylene chains. Individual geometric isomers of pyrimidinophanes were isolated. The structure of one of these isomers was established by X-ray diffraction analysis. Quaternization of the bridging N atoms with o-nitrobenzyl bromide gave rise to water-soluble pyrimidinophanes.     

Reaction of 1,2,4-triazole-3-thiones with 1-chloro-2,3-epoxypropane

Addition of 1-chloro-2,3-epoxypropane to 1,2,4-triazole-3-thiones depending on the ratio of the reactants leads to the formation of 3-(1-chloro-2-hydroxypropyl)-3-(1-chloro-2-hydroxypropylthio)-1,2,4-triazoles. 3-Hydroxy-1,2,4-triazolo[2,3-b] tetrahydro-1,3-triazines have been synthesized by intramolecular cyclization of the monoadducts.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 271–274, February, 1987     

1,3-二(乙氧基甲基)-5-N,N-二甲氨基-6-甲基尿嘧啶的合成

报道了1,3-二(乙氧基甲基)-5-N,N-二甲氨基-6-甲基尿嘧啶方便、高产率的合成方法. 以6-甲基尿嘧啶(1)为起始物, 经硝化、嘧啶N¹,N ³-烷基化、还原及氨基甲基化, 首次高产率合成了1,3-二(乙氧基甲基)-5- N,N -二甲氨基-6-甲基尿嘧啶(5), 并对其化学结构进行了表征.     

Synthesis of New 3-Phenoxypropan-2-ols with Various Heterocyclic Substituents

1-Phenoxy-3-piperidinopropan-2-ol, 1-(5-methyl-1,3-benzothiazol-2-ylsulfanyl)-3-phenoxypropan-2-ol, 1-(2-hydroxy-3-phenoxypropyl)azepan-2-one, 1,1′-(6-chloro-1,3-benzothiazol-2-ylimino)bis(3-phenoxypropan-2-ol), 1-(1,3-benzothiazol-2-ylsulfanyl)-3-phenoxypropan-2-ol, 1,1′-(piperazine-1,4-diyl)bis(3-phenoxypropan-2-ol), and 1,3-bis(2-hydroxy-3-phenoxypropyl)barbituric acid were synthesized by condensation of 1,2-epoxy-3-phenoxypropane with the corresponding amines and thiols.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 1, 2005, pp. 70–72.Original Russian Text Copyright © 2005 by Mesropyan, Ambartsumyan, Avetisyan, Galstyan, Arutyunova.     

Synthesis and reactions of 2-chloro-1,3-bis(trimethylsilyloxy)-1,3-butadienes

The reaction of 2-chloro-1,3-bis(trimethylsilyloxy)-1,3-butadienes with various electrophiles allows a convenient synthesis of chlorinated molecules which are not readily available by other methods.