2-(2-(5-氟尿嘧啶-1-基)乙酰氨基)丙酸的合成及表征

以5-氟尿嘧啶-1-基乙酸为原料,N,N-二异丙基碳二亚胺(DIC)/1-羟基苯并三氮唑(HOBt)为缩合剂,分别与L-丙氨酸甲酯和D-丙氨酸甲酯通过液相偶联合成了(S)-和(R)-2-(2-(5-氟-2,4-二氧-3,4-二氢嘧啶-1(2H) -基)乙酰氨基)丙酸甲酯对映体,收率分别为82％和80％;室温下将化合物水...     

2-fluoro-3-nitroaniline and 2-fluoro-1,3-phenylenediamine

2-Fluoro-3-nitroaniline (I), erroneously reported in the literature, has been synthesized by partial reduction of 2-fluoro-1,3-dinitrobenzene (II). Total reduction of (II) gives 2-fluoro-1,3-phenylenediamine (V). The NMR parameters of 1-fluoro-2,4-dinitrobenzene (IV), 2-fluoro-5-nitroaniline (III) and compounds (I), (II) and (V) are reported.     

Diastereoselective formation of 2-fluoro-2-trifluoromethyl-3,4-alkadienamides from propargyl alcohols and hexafluoropropene-diethylamine adduct (PPDA)

Treatment of propargyl alcohols (1) with hexafluoropropene-diethylamine adduct (PPDA) affords N,N-diethyl-2-fluoro-2-trifluoromethyl-3,4-alkadienamides (2) that are produced by the Claisen rearrangement of intermediary 2-alkynyl 1-(N,N-diethylamino)-2,3,3,3-tetrafluoro-1-propenyl ethers. Starting from propargyl alcohols bearing a triple bond at the terminal position, the corresponding products (2) were formed with a high stereoselectivity.     

Chemoenzymatic synthesis of 2-substituted 2-fluoro-1,3-dioxygenated chiral building blocks

A series of 2-substituted-2-fluoro-1,3-dioxygenated chiral building blocks are synthesized via a chemoenzymatic route using either (i) lipase catalyzed monohydrolysis of suitably functionalized malonic diesters, or (ii) lipase catalyzed monoacetylation of suitably functionalized 1,3-propanediols.     

Synthesis of carbon-14 labeled 1-acetoxyethyl 2-(2-fluoro-4-biphenyl)propionate (14C-FP 83)

1-Acetoxyethyl 2-(2-fluoro-4-biphenylyl) [14C-methyl]propionate (14C-Me-FP 83), a novel nonsteroidal antiinflammatory agent for injection, was synthesized in order to investigate the metabolic fate. 14C-Me-FP 83 was obtained by the condensation of 2-(2-fluoro-4-biphenylyl) [14C-methyl]propionic acid with 1-chloroethyl acetate. The chemical yield of 1 was 62% after purification. The specific activity was 258 kBq/mg (6.99 microCi/mg) and its radiochemical purity was 99% in thin layer chromatographic method.     

Synthesis and properties of N-(2-chloro-5-fluoro-4-pyrimidyl)- and N-(2-ethylthio-5-fluoro-4-pyridmidyl)-substituted amino acids

Synthetic routes to and the properties of N-(2-chloro-5-fluoro-4-pyrimidyl)- and N-(2-ethylthio-5-fluoro-4-pyrimidyl)-substituted amino acids are shown.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 258–261, February, 1971.     

Synthesis and structure of o-bis(2-fluoro-2,2-dinitroethyl)-nitromethyl ester of 2′-fluoro-2′, 2′-dinitroethyl-2″-fluoro-2″-nitroethylenecarboxime

Conclusions The product of conversion of O-bis(2-fluoro-2,2-dinitroethyl)nitromethylbis(2-fluoro-2,2-dinitroethyl)carboxime in methanol or ether is O-bis(2-fluoro-2,2-dinitroethyl)nitromethyl-2-fluoro-2,2-dinitroethyl-2'-fluoro-2-nitroethylenecarboxinie, the structure of which has been established by x-ray diffraction analysis.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 2019–2021, September, 1987.     

Lipase mediated preparation of differently protected homochiral 2-aryl-2-fluoro-1,3-propanediols

Lipase mediated asymmetric monohydrolysis of 2-aryl-2-fluoromalonic acid diesters or monoacetylation of 2-aryl-2-fluoro-1,3-propanediols affords chiral fluorinated polyfunctionalized C₃ synthons in excellent enantiomeric excess and acceptable chemical yields.     

Fused polycyclic nitrogen-containing heterocycles 21. Condensation of 4-hydroxy-3,5-diphenyl-2-phenyliminothiazolidine with 5-fluoro-4-morpholino- and 4-(4-methylpiperazino)-1,2-phenylenediamines

The condensation of 4-hydroxy-3,5-diphenyl-2-phenyliminothiazolidine with 5-fluoro-4-morpholino- and 5-fluoro-4-(4-methylpiperazino)-1,2-phenylenediamines leads to region-isomeric thiazolo[3,4-a]quinoxalines differing in substituents in positions 7 and 8 of the benzene ring. From the ratio of isomers formed it follows that the mesomeric effect of a fluorine atom in 1,2-phenylenediamines is comparable with the influence of an aminosubstituent.     

Synthesis of 3-fluoro-2-(trinitromethyl)-1-propanol

Conclusions 3-Fluoro-2-(trinltromethyl)-1-propanol nitrate, the acid hydrolysis of which resulted in 3-fluoro-2-(trinitromethyl)-1-propanol, was obtained by the direct fluorination of 2,4-bis(trinitromethyl)-4-mercuri-1,7-heptanediol.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 7, pp. 1650–1651, July, 1972.     

Stereoselective synthesis of (Z)-2-fluoro-1-alkenyl(phenyl)iodonium tetrafluoroborates

[reaction: see text] (Z)-2-Fluoro-1-alkenyl(phenyl)iodonium salts were stereoselectively prepared by the reaction of alkynyl(phenyl)iodonium salts with aqueous HF in good yields. The method is applicable to the synthesis of fluoroalkenyliodonium salts having functional groups such as ketone, ester, and chloride. (Z)-2-Fluoro-1-alkene, (Z)-2-fluoro-2-alkenoate, and (Z)-beta-fluoroenyne could be stereoselectively prepared from the fluoroalkenyliodonium salt.     

Thermal Isomerization of 2-Bromo-2-fluoro-1-alkylidenecyclopropanes in Polar Solvents

2-Bromo-2-fluoro-1-alkylidenecyclopropanes heated in polar solvents undergo isomerization into substituted 3-bromo-2-fluoro-1,3-butadienes. 2-Bromo-3-methyl-1-methylene-3-phenyl-2-fluorocyclopropane at heating afforded a mixture of substituted 1-(bromofluoromethylene)cyclopropane and isomeric 1-bromo-1-fluoro-1,3-butadienes.     

Convenient synthesis of enantiopure (R-) and (S-)-3-fluoro-3-aminomethylpyrrolidines

(R-)- and (S-)-3-fluoro-3-aminomethylpyrrolidines were synthesized from methyl α-fluoroacrylate in eight steps. α-Phenylethylamine was used as a chiral auxiliary to separate the racemic mixture. The overall synthesis yield was 31%.     

The new convenient synthesis of fluorinated Penciclovir analogues 9-(4-fluoro-3-hydroxymethylbutyl) guanine (FHBG) and 2-amino-6-fluoro-9-(4-hydroxy-3-hydroxymethylbutyl) purine (6-Fluoropenciclovir)

9-(4-Hydroxy-3-hydroxymethylbutyl) guanine (Penciclovir) is a potent and selective inhibitor of members of the herpes virus family. A new convenient synthesis of fluorinated Penciclovir analogues 9-(4-fluoro-3-hydroxymethylbutyl) guanine (FHBG) and 2-amino-6-fluoro-9-(4-hydroxy-3-hydroxy-methylbutyl) purine (6-Fluoropenciclovir) were described. The structures of the products were characterized by UV, IR, ¹H NMR, ¹⁹F NMR spectra and MS.     

Asymmetric Morita-Baylis-Hillman reaction of arylaldehydes with 2-cyclohexen-1-one catalyzed by chiral bis(thio)urea and DABCO

Novel bis(thio)urea organocatalysts were synthesized from axially chiral (R)-(-)-5,5',6,6',7,7',8,8'-octahydro-1,1'-binaphthyl-2,2'-diamine (H8-BINAM), and their catalytic abilities have been examined in the Morita-Baylis-Hillman reaction of 2-cyclohexen-1-one or 2-cyclopenten-1-one with a wide range of aromatic aldehydes in combination with DABCO. The best result was achieved in the reaction of 3-fluorobenzaldehyde with 2-cyclohexen-1-one to give the desired Morita-Baylis-Hillman product in 79% yield and 88% ee.     

Stereocontrolled access to α-fluoro-β-ketoesters

The effect of a fluorine atom on the asymmetric Michael reaction between a chiral α-fluoro-β-enaminoester derived from (S)-1-phenylethylamine and various electrophilic alkenes is studied. α-Fluoro-α-substituted ketoesters are obtained in good yields with fairly good enantioselectivity.     

Stereoselective synthesis of (Z)-β-fluoro-α,β-unsaturated esters from (Z)-2-fluoro-1-alkenyliodonium salts

(Z)-β-Fluoro-α,β-unsaturated esters were stereoselectively synthesized from (Z)-2-fluoro-1-alkenyliodonium salts by the Pd-catalyzed methoxycarbonylation reaction. The reaction proceeded at room temperature and various functional groups on the substrate can tolerate the reaction conditions.     

A new synthesis of 2-fluoro-1-naphthols

A general synthesis of 2-fluoro-1-naphthols in two steps from 1-indanones is reported. The 1-indanones are first converted to difluoromethyl 2-fluoro-1-napthyl ethers by reaction with difluorocarbene source, trimethylsilyl 2-fluorosulfonyl-2,2-difluoroacetate (TFDA). These ethers are then converted in high yield to the respective naphthols by heating with a mixture of acetic acid and 48% HBr.     

Fluorocarbohydrates-XXVIII: Synthesis and characterisation of 2-deoxy-2-fluoro-derivatives of l-rhamnose and l-epirhamnose

Addition of CF₃OF to 3,4-di-O-acetyl-l-rhamnal gave four products separable by fractional crystallisation and column chromatography. The two principal products were in the epirhamnose series, i.e. trifluoromethyl 3,4-di-O-acetyl-2,6-dideoxy-2-fluoro-α-l-glucoside and 3,4-di-O-acetyl-2,6-dideoxy-2-fluoro-α-l-glucosyl fluoride. The lesser products were in the rhamnose series viz. trifluoromethyl 3,4-di-O-acetyl-2,6-dideoxy-2-fluoro-β-1-mannoside and 3,4-di-O-acetyl-2,6-dideoxy-2-fluoro-β-l-mannosyl fluoride. The structures were confirmed by ¹H and ¹⁹F NMR spectral measurements. Deacylation and acidic hydrolysis gave the free 2-deoxy-2-fluoro sugars of both series.     

Molecular structure of 1-phenyl-1-fluoro-5-methylquasisilatrane (2-phenyl-2-fluoro-1,3-dioxa-6-aza-6-methyl-2-silacyclooctane)

The crystal and molecular structure of 1-phenyl-1-fluoro-5-methylquasisilatrane PhFSi(OCH₂CH₂)₂NMe was investigated by X-ray diffraction at 100 K. The coordination polyhedron of the silicon atom in the molecule is a slightly distorted trigonal bipyramid containing fluorine and nitrogen atoms in the axial positions and two endocyclic oxygen atoms and the carbon atom of the phenyl group at three vertices of the equatorial plane.