Condensed Isoquinolines. 15. Synthesis of 5,10-Dihydro[1,2,4]triazolo[1,5-b]isoquinolines and Related Spiranes

Condensation of o-bromomethylphenylacetonitrile with arylcarbohydrazides gave, depending on the reaction conditions, 2-arylcarboxamido-1,4-dihydroisoquinoline-3(2H)-imine hydrobromides or 2-aryl-5,10-dihydro[1,2,4]triazolo[1,5-b]isoquinolines. Analogous condensation of 4-(2-bromomethylphenyl)tetrahydro-2H-pyran-4-carbonitrile and 1-(2-bromomethylphenyl)-1-cyclopentanecarbonitrile with arylcarbohydrazides gave respectively 2-aryl-2,3,5,6-tetrahydrospiro[4H-pyran-4,10'(5'H)-[1,2,4]triazolo[1,5-b]isoquinolines and 2-arylspiro[1,2,4]triazolo[1,5,b]isoquinoline-10(5'H)-1'-cyclopentanes, derivatives of new spirane heterocycles. The reaction with condensing agents of 3-imino-2,2',3,3'5',6'-hexahydrospiro[isoquinoline-4(1H),4'-4H-pyran]-2-amine and 3-imino-2,3-dihydrospiro[isoquinoline-4(1H),1'-cyclopentane]-2-amine hydrobromides, synthesized from the corresponding bromo nitriles and hydrazine, may serve as an alternative route for the synthesis of these compounds. The structure of obtained triazoloisoquinolines was established from IR, ¹H and ¹³C NMR spectra. An X-ray crystallographic study of 2-phenylspiro[1,2,4]triazolo[1,5-b]isoquinoline-10(5H),1'-cyclopentane was carried out.     

Condensed Isoquinolines. 14. Spirocyclic Systems Containing a Benzo[5,6][1,2,4]thiadiazino[4,3-b]isoquinoline Ring

We propose a convenient preparative method for synthesis of derivatives of novel heterospirane systems with a benzo[5,6][1,2,4]thiadiazino[4,3-b]isoquinoline ring, based on the reaction of 1-(2-bromomethylphenyl)-1-cyclopentanecarbonitrile and 4-(2-bromomethylphenyl)-3,4,5,6-tetrahydro-2H-pyran-4-carbonitrile with o-aminobenzenesulfamide.     

Condensed Isoquinolines. 12. Synthesis of Novel Heterocyclic Systems Containing a Partially Hydrogenated Spiro[isoquinoline-4,4'-(2H)-pyran] Fragment

By condensation of 4-(2-bromomethyl)-3,4,5,6-tetrahydro-2H-pyran-4-carbonitrile with anthranilic acid, its derivatives substituted in the benzene ring (esters, nitrile), and with esters of 2-aminothiophene-3-carboxylic acids and 3-amino-5-bromobenzofuran-2-carboxylic acid there have been synthesized novel derivatives which include spiro-linked tetrahydropyran and 5,10-dihydro-3H-pyrimido[1,2-b]isoquinoline fragments. The pyrimidine ring of the latter was annelated by a substituted benzene, thiophene, or 5-bromobenzofuran ring.     

Condensed Isoquinolines. 10. Borohydride Reduction in the 5H-Isoquino[2,3-a]quinazolin-5-one Series

Borohydride reduction in a series of 7-benzyl- and newly synthesized 7-arylmethylene-7,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-ones leads stereoselectively to erythro-7-benzyl-6,6a,7,12-tetrahydro-5H-isoquino[2,3-a]quinazolin-5-ones. 7,7-Disubstituted 7,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-ones are inert to the action of sodium borohydride, but spiro[5H-isoquino[2,3-a]quinazolin-7(12H),2'-indane]-5-one is reduced under rigid conditions to 6,6a-dihydrospiro[5H-isoquino[2,3-a]quinazolin-7(12H),2'-indan]-5-one. 7-Acetyl- and 7-benzoyl-6,11-dihydro-5H-isoquino[2,3-a]quinazolin-5-ones are converted in an aqueous alcoholic solution of sodium borohydride to the previously described 6,6a,7,12-tetrahydro-5H-isoquino[2,3-a]quinazolin-5-one. The structure and special features of the conformational behavior of the reduction products obtained were demonstrated by ¹H NMR spectroscopy.!     

Condensed isoquinolines. 19. Synthesis of 1′-R-spiro[6a,11b-diazabenz[e]aceanthrylene-6(7H),4′ (1′H)-pyridine]-5,7(12H)-diones

During acylation of 7-isonicotinoyl-6,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-one or its alkylation followed by treatment with organic bases, spirocyclization occurs with formation of derivatives of a novel heterocyclic system: 1′-acyl-and 1′-alkylspiro[7H,12H-6a,11b-diazabenz[e]aceanthrylene-6(5H),4′(1′ H)-pyridine]-5,7-diones. We have studied the spectral properties of the synthesized spirans. We have shown that 7-nicotinoyl-6,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-one does not undergo an analogous reaction of repeated acylation, while treatment of its quaternary salt with bases leads to a complex mixture of unidentified products. For Communication 18, see [1]. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 113–122, January, 2006.     

Condensed Pyridopyrimidines. 7. Synthesis of Condensed Triazolo[4,3-c]- and Tetrazolo[1,5-c]pyrimidines

Novel dihydro-5H-pyrano[3',4':5',6']pyrido[2,3-d]-1,2,4-triazolo[4,3-c]pyrimidines and 1,2,3,4-tetrazolo[1,5-c]pyrimidines have been synthesized from 2-amino-3-cyano-7,7-dimethyl-7,8-dihydro-5H-pyrano[4,3-b]pyridine.     

Palladium-Catalyzed Asymmetric [4+2] Cycloaddition of 2-Methylidenetrimethylene Carbonate with Alkenes: Access to Chiral Tetrahydropyran-Fused Spirocyclic Scaffolds

A palladium-catalyzed asymmetric [4+2] cycloaddition of 2-methylidenetrimethylene carbonate with alkenes derived from pyrazolones, indandione, or barbiturate has been successfully developed, affording pharmacologically interesting chiral tetrahydropyran-fused spirocyclic scaffolds. The target compounds were generated in good to excellent yields and with high enantioselectivity (up to 99 % ee). Furthermore, this cycloaddition reaction could be efficiently scaled up, and several synthetic transformations were accomplished for the construction of other useful chiral spiropyrazolone and spiroindandione derivatives.     

Synthesis and Antiviral Properties of Spirocyclic [1,2,3]‐Triazolooxazine Nucleosides

An efficient synthesis of spirocyclic triazolooxazine nucleosides is described. This was achieved by the conversion of β‐D ‐psicofuranose to the corresponding azido‐derivative, followed by alkylation of the primary alcohol with a range of propargyl bromides, obtained by Sonogashira chemistry. The products of these reactions underwent 1,3‐dipolar addition smoothly to generate the protected spirocyclic adducts. These were easily deprotected to give the corresponding ribose nucleosides. The library of compounds obtained was investigated for its antiviral activity using MHV (mouse hepatitis virus) as a model wherein derivative 3 f showed the most promising activity and tolerability.     

氰基亚胺与亚甲基二氢苯并呋喃二酮类化合物的[3+2]环加成反应:螺吡唑类化合物的合成

采用具有环外双键的二氢苯并呋喃二酮类化合物和氰基亚胺的[3+2]环加成反应,在温和条件下,以高产率(78%~94%)和高非对映选择性(>20∶1dr)构建了一系列具有螺环结构的吡唑类化合物.     

Isocyanide‐Based Multicomponent Reactions: Concise Synthesis of Spirocyclic Oxindoles with Molecular Complexity by Using a [1,5]‐Hydrogen Shift as the Key Step

A concise multicomponent reaction of isocyanide, α‐substituted allenoate, and methyleneindolinone has been disclosed. This protocol provides a fast and straightforward approach to synthesize unusual tricyclic oxindoles in an efficient and atom‐economic manner. Mechanistically, the present cycloaddition may proceed through a cascade sequence involving double Michael addition, double cyclization, double [1,5]‐hydrogen shift, and group migration. The introduction of a special alkyl group to the allenoate is believed to play a key role in the cascade reaction. This method also features a broad substrate scope, which is particularly useful for the delivery of a large number of compounds.     

Derivatives of Condensed Thienopyrimidimines. 13. Synthesis and Structure of Pyrano[4',3':4,5]thieno[3,2-e]-1,2,4-triazolo[2,3-c]pyrimidines

Methods for the synthesis of 5-substituted 10,10-dimethyl-10,11-dihydro-8H-pyrano[4',3':4,5]thieno[3,2-e]-1,2,4-triazolo[2,3-c]pyrimidines have been developed. An X-ray crystallographic study of 5-(2-ethoxymethylhydrazino)-10,10-dimethyl-10,11-dihydro-8H-pyrano[4',3':4,5]thieno[3,2-e]-1,2,4-triazolo[2,3-c]pyrimidine has been carried out.     

7-(羟甲基)-8-氮杂螺[4.5]癸烷-8-羧酸叔丁酯的合成

以8-氮杂螺[4.5]癸烷-7,9-二酮为原料,通过酰胺还原、N-Boc保护、甲酰化、醛基四步反应还原反应合成得到目标化合物7-(羟甲基)-8-氮杂螺[4.5]癸烷-8-羧酸叔丁酯,总收率29.8％.反应中间体及产物结构经1 H NMR和ESI-MS确证,同时对每步反应条件进行讨论.该研究提供了一种新结构的含氮螺环化合...     

Synthesis of 1,2,3,4-tetrazino[5,6-g]benzo-1,2,3,4-tetrazine 1,3,7,9-tetraoxides

1,2,3,4-Tetrazino[5,6-g]benzo-1,2,3,4-tetrazine 1,3,7,9-tetraoxides, which possess an-thracene-type annulation of the benzene ring with two 1,2,3,4-tetrazine 1,3-dioxide fragments, were obtained for the first time from aminobenzenes containing tert-butyl-NNO-azoxy groups in appropriate positions. Complete assignments of the signals in the ¹H, ¹³C, and ¹⁴N NMR spectra of the compounds obtained were carried out. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1595–1599, September, 2006.     

Synthesis and stereochemical studies of 1- and 2-phenyl-substituted 1,3-oxazino[4,3-a]isoquinoline derivatives

Starting from the 1′- or 2′-phenyl-substituted 1-(2′-hydroxyethyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline diastereomers 3 and 6, 4-unsubstituted and 4-(p-nitrophenyl)- and 4-oxo-substituted 1-phenyl- and 2-phenyl-9,10-dimethoxy-2H,4H-1,6,7,11b-tetrahydro-1,3-oxazino[4,3-a]isoquinolines (7-12) were prepared. The relative configurations and the predominant conformations of the products were determined by NMR spectroscopy, by quantum chemical calculations and, for (2R^∗,4S^∗,11bR^∗)-9,10-dimethoxy-4-(p-nitrophenyl)-2-phenyl-2H,4H-1,6,7,11b-tetrahydro-1,3-oxazino[4,3-a]isoquinoline (11), by X-ray diffraction.     

Synthesis of 2- and 3-substituted-1,2,3,4-tetrahydrodibenzo[f,h]isoquinolines

Some 2- and 3-substituted-1,2,3,4-tetrahydrodibenzo[f,h]isoquinolines were prepared by a synthetic scheme involving a selective Borch reduction of an amide to the corresponding amine and a Friedel-Crafts cyclization to obtain the dibenzo[f,h]isoquinoline system. The title compounds, which have a similarity to the cell growth inhibitory alkaloid cryptopleurine, failed to exhibit significant protein synthesis inhibitory activity.     

Heck-mediated synthesis and photochemically induced cyclization of [2-(2-styrylphenyl)ethyl]carbamic acid ethyl esters and 2-styryl-benzoic acid methyl esters: total synthesis of naphtho[2,1f]isoquinolines (2-azachrysenes)

We describe two new closely related total syntheses of naphtho[2,1-f]isoquinolines. The first synthesis consists of a Heck coupling reaction between trifluoromethanesulfonic acid 2-(2-ethoxycarbonylaminoethyl)phenyl esters and styrenes to give [2-(2-styrylphenyl)ethyl]carbamic acid ethyl esters. These compounds cyclize to give (2-phenanthren-1-yl-ethyl)carbamic acid ethyl esters, from which 2-azachrysenes can be obtained in a three-step sequence. The second synthesis includes a new total synthesis of 2-styrylbenzoic acid methyl esters by Heck coupling of methyl o-iodobenzoates to styrenes, followed by the transformation of the resulting benzoic acid derivatives into phenanthrene-1-carboxylic acid methyl esters and then into the target compounds by a six-step sequence including a Bischler-Napieralski cyclization.     

Derivatives of Condensed Pyridopyrimidines. 3. Synthesis of Condensed Imidazo[4,5-b]pyridine and also 4-Oxo- and 2,4-Dioxopyrido[2,3-d]pyrimidines

A convient methods has been developed for the synthesis of condensed imidazo[4,5-b]pyridine and also 4-oxo- and 2,4-dioxopyrido[2,3-d]pyrimidines. The optimum conditions for the Curtius rearrangement of 2-amino-3-azidocarbonyl derivative of pyrano[4,3-b]pyridine have been established.