Synthesis of 9-alkyl-8-methoxy-8-methyl-1,3,6-trioxo-2,7-diazaspiro[4.4]nonane-4-carbonitriles

A method of synthesis of 9-alkyl-8-methyl-8-methoxy-1,3,6-trioxo-2,7-diazaspiro[4.4]nonane-4-carbonitriles consisting in the reaction of 3-amino-8-hydroxy-1,6-dioxo-2,7-diazaspiro[4.4]non-3-ene-4-carbonitriles with methanol in the presence of sulfuric acid was developed.     

Reduction of 7-aryl-6,8-dioxo-2-oxa-3,7-diazabicyclo[3.3.0]oct-3-ene-4-carboxylic and 7-aryl-6,8-dioxo-1-oxa-2,7-diazaspiro[4.4]non-2-ene-3-carboxylic acid esters

Ethyl 7-aryl-6,8-dioxo-2-oxa-3,7-diazabicyclo[3.3.0]oct-3-ene-4-carboxylates and ethyl 7-aryl-6,8-dioxo-1-oxa-2,7-diazaspiro[4.4]non-2-ene-3-carboxylates were selectively reduced with sodium tetrahydridoborate at the carbonyl group in the β-position with respect to the oxygen atom in the isoxazole ring.     

合成2-丁基-1,3-二氮杂螺[4.4]壬-1-烯-4-酮的工艺改进

以1-氨基环戊腈草酸盐为起始原料,经双氧水水解、戊酰氯酰化、环合制得厄贝沙坦的关键中间体——2-丁基-1,3-二氮杂螺[4.4]壬-1-烯-4-酮,总产率80.9%,其结构经1H NMR,13C NMR和MS确证。     

A stereoselective synthetic route to 1,6-Dioxaspiro[4.4]non-3-en-2-ones from cyclopropyl alkyl ketones and alpha-ketoesters

[reaction: see text] The SnCl(4)-mediated reactions of cyclopropyl alkyl ketones with alpha-ketoesters afford a novel method for the synthesis of 1,6-dioxaspiro[4.4]non-3-en-2-ones with high stereoselectivities in moderate to good yields. This process is a sequential reaction involving a nucleophilic ring-opening reaction of the cyclopropane by H(2)O, an aldol-type reaction, and a cyclic transesterification mediated by Lewis acid.     

Synthesis and Crystal Structure of 2-Methoxy-benzoic Acid 2-Oxo-3-（2,4,6-trimethyl-phenyl）-1-oxa-spiro[4.4]non-3-en-4-yl Ester

The new title compound 2-methoxy-benzoic acid 2-oxo-3-(2,4,6-trimethyl-phenyl)-1-oxa-spiro[4.4]non-3-en-4-yl ester(3,C25H26O5) has been synthesized by the condensation reaction of 4-hydroxy-3-(2,4,6-trimethyl-phenyl)-1-oxa-spiro[4.4]non-3-en-2-one(2) with 2-methoxylben-zoyl chloride,and characterized by 1H NMR and MS spectra.Its crystal structure was determined by single-crystal X-ray diffraction.The crystal is of monoclinic,space group P21/c with a = 10.6945(7),b = 12.8176(7),c = 16.4223(10) ,β = 103.5665(17)o,V = 2188.3(2) 3,Z = 4,Dc = 1.234 g/cm3,F(000) = 864.000,μ = 0.085 mm-1,the final R = 0.0520 and wR = 0.1132 for 2732 observed reflections with I 2σ(I).In the crystal structure,the C(1)-C(2)(1.478 ) bond is significantly shorter than the normal single C-C bond(1.53 ),suggesting that the carbonyl group on C(1) has formed a conjugated system with a double bond on C(2) and C(12).     

One-step synthesis of substituted 2-amino-4H-chromenes and 2-amino-4H-benzo[f]chromenes. Molecular and crystal structure of 2-amino-3-cyano-6-hydroxy-4-phenyl-4H-benzo[f]chromene

Substituted 2-aminochromenes were synthesized by three-component condensation of aromatic aldehydes, derivatives of cyanoacetic acid, and phenols or naphthols. The molecular and crystal structure of 2-amino-3-cyano-6-hydroxy-4-phenyl-4H-benzo[f]chromene was established by X-ray diffraction analysis.     

Synthesis of Novel Isoxazolyl 1,6-Dithia-4,9-diazaspiro[4,4]nonane-3,8-diones and 1-Oxa-6-thia-2,4,9-triazaspiro[4,4]non-2-ene-8-ones

The key intermediates, 3-(5-methyl-3-isoxazolyl)-2-arylimino-1,3-thiazolan-4-ones (3), were obtained from 3-amino-5-methylisoxazole (1) by reaction with chloroacetyl chloride followed by treatment with aryl isothiocyanates. Cyclocondensation of 3 with mercapto acetic acid furnished novel isoxazolyl 1,6-dithia-4,9-diazaspiro[4,4]nonane-3,8-diones (4). Cycloaddition of 3 with benzonitrile oxides afforded novel isoxazolyl 1-oxa-6-thia-2,4,9-triazaspiro[4,4]non-2-ene-8-ones (5).     

Synthesis of substituted 2-amino-3-cyano-4-methylpyrroles

A facile route for the synthesis of substituted 2-amino-3-cyano-4-methylpyrroles from N-acetyl-α-amino ketones and malononitrile is reported.     

Prostanoids. LXXVIII. New sp2-Functionalized 4-Hydroxy-2-cyclopentenones from 6,7-Dichloro-1,4-dioxaspiro[4.4]non-6-en-8-one

Readily accessible 6,7-dichloro-1,4-dioxaspiro[4.4]non-6-en-8-one was converted into 2,3-dichloro-, 2-ethylthio-, and 3-chloro-2-ethylthio-4-hydroxy-2-cyclopentenones.     

Synthesis and chemical diversity analysis of bicyclo[3.3.1]non-3-en-2-ones

Functionalized bicyclo[3.3.1]non-3-en-2-ones are obtained from commercially available phenols by a hypervalent iodine oxidation, enone epoxidation, epoxide thiolysis, and intramolecular aldol reaction sequence. Reaction optimization studies identified room temperature as well as microwave-mediated procedures, providing moderate to good yields (57-88%) in the thiophenol-mediated epoxide opening and intramolecular aldol reaction. In addition, the isolation of a key intermediate and in situ NMR studies supported the mechanistic hypothesis. The bicyclic ring products occupy novel chemical space according to ChemGPS and Chemaxon chemical diversity and cheminformatics analyses.     

Synthesis of substituted 2-amino-3-cyano-7,9-dimethyl-4H-pyrano[2",3":4,5]thieno[2,3-b]pyridines

4,6-Dimethyl-2H-thieno[2,3-b]pyridin-3-one reacts with 2-aryl-1,1-dicyanoethylenes or an aromatic aldehyde/ketone (cyclohexanone and piperidone derivatives) and malononitrile to give substituted 2-amino-3-cyano-7,9-dimethyl-4H-pyrano[2",3":4,5]thieno[2,3-b]pyridines.     

Synthesis of homochiral spiro[4.4] nonane-1,6-diols

Homochiral cis,cis-; cis,trans- and trans,trans-spiro[4.4]nonane-1,6-diols were prepared via diastereoselective reduction of enantiomerically pure spiro[4.4]nonane-1,6-dione (1) with the corresponding reducing agents: lithium n-butyldiisobutylaluminium hydride for cis,cis-diol (2) with 88% yield; BH3·THF for cis, trans-diol (3) with 91% yield; LiAlH4 for trans,trans-diol (4) with 15% yield.     

Synthesis of substituted 3-amino-4-cyano-1-oxo-1,2,5,10-tetrahydroazepino [3,4-b]indoles

The preparation of 3-amino- and 3-dialkylamino-4-cyanoazepino[3,4-fc]indoles bearing substituents on the aromatic nucleus and N¹⁰ is outlined. Starting from suitable substituted ethyl 3-formylindole-2-carboxy-latcs 2 , condensation with malononitrile ( 3 ) and subsequent sodium borohydride-reduction yielded ethyl 3-(2,2-dicyanoethyl)indole-2-carboxylates 5 and 19 , respectively, which were cyclized in boiling alkoxides to 3-alkoxy-4-cyanoazepino[3,4-b]indoles 10,11,20 and 21 . This sequence constitutes a novel and flexible route to functional azepino[3,4-b>]indoles. The aminolysis of 10,11,20 and 21 with different amines and ammonia yielded the title compounds which were screened for their possible biological activity.     

Regioselective conversion of 3-cyano-6-hydroxy-2-pyridones into 3-cyano-6-amino-2-pyridones

The reaction of a tautomeric mixture of 1-butyl-1,2-dihydro-6-hydroxy-4-methyl-2-oxopyridine-3-carbonitrile and its 2-hydroxy-6-oxo analog with phosphorus oxychloride gave 1-butyl-6-chloro-1,2-dihydro-4-methyl-2-oxopyridine-3-carbonitrile (68%) and 1-butyl-2-chloro-1,6-dihydro-4-methyl-6-pyridine-3-car-bonitrile (3%). Both chloropyridones were converted to their corresponding aminopyridones by reaction with liquid ammonia. Strong support for the molecular structure of 6-amino-1-butyl-1,2-dihydro-4-methyl-2-oxopyridine-3-carbonitrile was obtained on the basis of nmr techniques.     

Synthesis and Crystal Structure of 5-Amino-4-cyano-8-isobutyl-7-isopropyl-6-thiocarbamoyl-2-azabicyclo[2.2.2]oct-5-en-3-thione

5-Amino-4-cyano-8-isobutyl-7-isopropyl-6-thiocarbamoyl-2-azabicyclo[2.2.2]oct-5-en-3-thione was synthesized by the condensation of isovaleryl aldehyde with cyanothioacetamide. The structure of the product was established by X-ray crystallography.     

Synthesis,dimerization, and oligomerization of 5-silaspiro[4.4]non-2-ene

Synthesis of 5-silaspiro[4.4]non-2-ene and its low-temperature anionic polymerization with the ring opening have been accomplished. A dimer and cyclic oligomers with higher degree of polymerization are predominantly formed under the action of BuⁿLi in THF at −78 °C.