Facile Regioselective Synthesis of 2-Methyl Furo [3,2-c][1] benzopyran-4-one 2-Methyl Furo[2,3-c] [1]benzopyran-4-one

The title compounds (7 &8) were obtained in excellent yields from 4-[2′-chloroprop-2′-enyloxy] [1] benzopyran-2-one (5) and 3-[2′-chloroprop-2-enyloxy][1]benzopyran-2-one (6) via [3,3] sigmatropic rearrangement and cyclisation of the intermediate chloroallylic enols with conc. H₂SO₄. The reaction was also studied in N,N-dimethyl aniline.     

Design and Synthesis of 3,4-Dihydropyrrolo[2, 1-c][1, 4]oxazin-1-oneand its 7-Acyl Derivatives

Starting from 1H-pyrrole, unreported 3, 4-dihydropyrrolo[2, 1-c][l, 4]oxazin-1-one 4, 7-(4-chlorobenzoyl)-3, 4-dihydropyrrolo[2, 1-c][1, 4]oxazin-1-one 5 and 7-benzoyl-3, 4-dihydro-pyrrolo [2, 1-c][1, 4]oxazin-1-one 9 were designed and synthesized. They may have antipyretic and analgesic activities.     

Diastereoselective Pictet-Spengler approach for the synthesis of pyrrolo[3,2-e][1,4]diazepin-2-one peptide turn mimics

Sixteen pyrrolo[3,2- e][1,4]diazepin-2-ones 1 were synthesized in 4-5 steps and 5-48% overall yields from 4-oxoproline 8 by a route featuring a diastereoselective Pictet-Spengler reaction to close the seven-membered diazepinone ring. Crystallographic analysis of pyrrolo[3,2- e][1,4]diazepin-2-one 1b by X-ray diffraction demonstrated that the alpha-amino acid residue adopted dihedral angle geometry similar to an ideal gamma-turn, illustrating the potential for employing these novel heterocycles as peptide turn mimics.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 3 . 12-Methylbenzo[h][1]benzothieno[2,3-c][1,6]naphthyridine

The synthesis of the 12-methyl derivative of a novel heterocyclic ring system, namely benzo[h][1]benzothieno[2,3-c][1,6]naphthyridine ( 8 ) was prepared by photocyclization of 3-chloro-N-(2′-methyl-4′-quinolyl)benzo-[6]thiophene-2-carboxamide ( 5 ) to 12-methylbenzo[h][1]benzothieno[2,3-c][1,6]naphthyridin-6(5H)-one ( 6 ). Chlorination of 6 afforded 6-chloro-12-methylbenzo[h][1]benzothieno[2,3-c][1,6]naphthyridine ( 7 ) which upon dechlorination provided the novel title compound 8 .     

Synthesis and cytotoxic activity of acronycine analogues in the benzo[c]pyrano[3,2-h]acridin-7-one and naphtho[1,2-b][1,7] and [1,10]-phenanthrolin-7(14H)-one series

Condensation of 1-bromo-2-naphthalenecarboxylic acid (9) with 7-methoxy-2,2-dimethyl-2H-1-benzopyran-5-ylamine (13) followed by acid-mediated cyclization afforded 6-methoxy-3,3-dimethyl-3,14-dihydro-7H-benzo[c]pyrano[3,2-h]acridin-7-one (15), which was further methylated into 6-methoxy-3,3,14-trimethyl-3,14-dihydro-7H-benzo[c]pyrano[3,2-h]acridin-7-one (benzo[c]acronycine) (3) and 6,7-dimethoxy-3,3-dimethyl-3H-benzo[c]pyrano[3,2-h]acridine (4). Osmium tetroxide oxidation of 15 gave the (+/-)-cis-diol 16, which afforded the benzopyranoacridine and benzopyranoacridone esters 17-22 upon acylation. Condensation of 9 with suitable aminoquinolines 23-25 afforded the carboxylic naphthylquinolylamines 26-28. Cyclization gave the corresponding naphtho[1,2-b][1,10]-phenanthrolin-7(14H)-ones 29 and 30, and naphtho[1,2-b][1,7]-phenanthrolin-7(14H)-one 31, which were subsequently N-methylated to the desired 14-methylnaphtho[1,2-b][1,10] and [1,7]-phenanthrolinones 6, 7, and 8. Benzo[c]pyrano[3,2-h]acridin-7-one derivatives 3, 16, and 22 displayed cytotoxic activities within the same range of magnitude as acronycine itself, whereas 7-alkoxybenzo[c]pyrano[3,2-h]acridine and 7-acyloxybenzo[c]pyrano[3,2-h]acridine derivatives 4 and 17-21 were less active when tested against L1210 murine leukemia cells in vitro. Naphthophenanthrolinones 6-8 were devoid of significant antiproliferative activity, but compounds 29-31 bearing no substituent on the nitrogen atom at position 14 were more potent.     

Synthesis of 1-methyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazin-4(3H)-one 2,2-dioxide

The reaction of methyl 2-bromo-6-(trifluoromethyl)-3-pyridinecarboxylate ( 1 ) with methanesulfonamide gave methyl 2-[(methylsulfonyl)amino]-6-(trifluoromethyl)-3-pyridine-carboxylate ( 2 ). Alkylation of compound 2 with methyl iodide followed by cyclization of the resulting methyl 2-[methyl(methylsulfonyl)amino]-6-(trifluoromethyl)-3-pyridinecarboxylate ( 3 ) yielded 1-methyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazin-4(3H)-one 2,2-dioxide ( 4 ). The reaction of compound 4 with α,2,4-trichlorotoluene, methyl bromopropionate, methyl iodide, 3-trifluoromethylphenyl isocyanate, phenyl isocyanate and 2,4-dichloro-5-(2-propynyloxy)phenyl isothiocyanate gave, respectively, 4-[(2,4-dichlorophenyl)methoxy]-1-methyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazine 2,2-dioxide ( 5 ), methyl 2-[[1-methyl-2,2-dioxido-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazin-4-yl]oxy]propanoate ( 6 ), 1,3,3-trimethyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazin-4(3H)-one 2,2-dioxide ( 7 ), 4-hydroxy-1-methyl-7-(trifluoromethyl)-N-[3-(trifluoromethyl)phenyl]-1H-pyrido[2,3-c][1,2]thiazine-3-carboxamide 2,2-dioxide ( 8 ), 4-hydroxy-1-methyl-7-(trifluoromethyl)-N-phenyl-1H-pyrido[2,3-c][1,2]thiazine-3-carboxamide 2,2-dioxide ( 9 ) and N-[2,4-dichloro-5-(2-propynyloxy)phenyl]-4-hydroxy-1-methyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2] thiazine-3-carboxamide 2,2-dioxide ( 10 ).     

Synthesis of 4H-[1]benzopyrano[3,4-c][1,2,5]thyadiazol-4-one and its reactions with some nucleophilic and electrophilic agents

The reaction of 3,4-diaminocoumarin with thionyl chloride gave 4H-[1]benzopyrano[3,4-c][1,2,5]thiadiazol-4-one (II), which was cleaved by the action of nucleophilic agents to the corresponding 4-(2-hydroxyphenyl)-1,2,5-thiadiazole-3-carboxylic acid derivatives. The nitration of II leads to the 8-nitro or 6,8-dinitro derivative; the latter was isolated in the form of 4-(2-hydroxy-3,5-dinitrophenyl)-1,2,5-thiadiazole-3-carboxylic acid.See [3] for our preliminary communication.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 977–981, July, 1988.     

4H-吡啶并[3,2-e][1,3]噻嗪-4-酮嘧啶衍生物的合成

2-氯烟酸异硫氰酸酯在碱性介质中与取代2-氨基嘧啶反应直接得到4H-吡啶并[3,2-e][1,3]噻嗪-4-酮嘧啶. 所合成的6个未见文献报道的目标化合物经IR, ¹H NMR和元素分析证实了其结构, 并对反应可能机理进行了探讨.     

Synthesis of (1H)-3,4-Dihydropyrrolo[2,1-c][1,4]oxazin-1-one Derivatives

It has been found that some acyl derivatives of 1,2,3,4-tetrahydro-1-indolizin-1-one 1and (1H)-3,4-dihydropyrrolo[1,2-a]pyrazin-1-one 2 show remarkable anti-inflammatory and analgesic activities1,2. The interest in extending the study of structure-activity relationships and search of new potent anti-inflammatory and analgesic agents led us to design and synthesize (1H)-3,4-dihydropyrrolo[2,1-c][1,4]oxazin-1-one 3 derivatives. NO 1 NNHO2 87654321ONO3 A few examples of the p…     

A synthesis of 4H-thieno[3,2-c][1]benzopyran-4-ones by an application of the salicylidene-thiolactone rearrangement

Salicylidenes prepared from 5-ethyl-4-thiolen-2-one undergo base-catalyzed rearrangement (salicylidene-thiolactone rearrangement) to 4H-thieno[3,2-c][1]benzopyran-4-ones.     

Synthesis of 5H-benzimidazo[1,2-a][1,3,4]thiadiazolo[2,3-d][1,3,5]triazin-5-one and 12H-benzimidazo[1,2-a]pyrimido[6,1-d][1,3,5]triazin-12-one,two new heterocyclic ring systems

2-(2,6-Dimethylpyrimidin-4-ylaminobenzimidazole) (VIIa) and 2-(1,3,4-thiadiazol-2-ylamino)benzimidazole (VIIb) underwent a ring-closure reaction with phosgene giving 1,3-dimethyl-12H-benzirnidazo[1,2-a]pyrirnido[6,1][-d][1,3,5]triazin-12-one (IIa) and 5H-benzimidazo[1,2-a][1,3,4]thiadiazolo[2,3-d][1,3,5]triazin-5-one (IIb) two hitherto unknown heterocyclic systems. A convenient synthesis of 2,6-dimethyl-4-aminopyrimidine is described.     

Properties of 4H-[1]benzopyrano[3,4-c]-[1,2,5]-selenodiazol-4-one

4H-[1]benzopyrano[3,4-c][1,2,5]selenodiazol-4-one has been synthesized by the reaction of 3,4-diaminocoumarin with selenous acid and its reaction with several nucleophiles (alkali, ammonia, amines, hydrazine hydrate) and its nitration have been studied. Using PMR spectroscopy, a comparative kinetic study of the opening of the lactone ring in 6,8-dinitro-4H-[1]benzopyrano[3,4-c][1,2,5]seleno- and thiadiazol-4-ones has been carried out.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 128–133, January, 1991.     

Novel heterocycles. Synthesis of 2,3-dihydro-6-methyl-2-phenyl-4H,6H-pyrano[3,2-c][2,1]benzothiazin-4-one 5,5-dioxide and related compounds

The reaction of 2-chloro-4-(methylsulfonyl)benzoyl chloride ( 5 ) with 1-methyl-1H-2,1-benzothiazin-4-(3H)-one 2,2-dioxide ( 4 ) gave the O-benzoyl compound, 1-methyl-2,2-dioxido-1H-2,1-benzothiazin-4-yl 2-chloro-4-(methylsulfonyl)benzoate ( 6 ), which rearranged to give the C-benzoyl isomer, [2-chloro-4-(methylsulfonyl)phenyl] (4-hydroxy-1-mefhyl-2,2-dioxido-1H-2,1-benzothiazin-3-yl)methanone ( 7 ). The O-cinnamoyl compound 13 that resulted from the addition of 2,4-dichlorocinnamoyl chloride ( 11 ) to compound 4 rearranged to give the C-cinnamoyl compound, 3-(2,4-dichlorophenyl)-1-(4-hydroxy-1-methyl-2,2-dioxido-1H-2,1-benzothiazin-3yl)-2-propen-1-one ( 15 ). On the other hand, 1-methyl-2,2-dioxido-1H-2,1-benzothiazin-4-yl 3-phenyl-2-propenoate ( 19 ) (from cinnamoyl chloride ( 17 ) and compound 4 ) rearranged to give 2,3-dihydro-6-methyl-2-phenyl-4H,6H-pyrano[3,2-c][2,1]benzothiazin-4-one 5,5-dioxide ( 21 ), an example of a hitherto unknown ring system. Additional examples of this novel heterocycle were prepared from 1-methyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazin-4(3H)-one 2,2-dioxide ( 23 ) and 1-methyl-1H-thieno[3,2-c][1,2]thiazin-4(3H)-one 2,2-dioxide ( 8 ).     

Pyrrolo[3,2-e][1,4]diazepin-2-one synthesis: a head-to-head comparison of soluble versus insoluble supports

Aryldiazepin-2-ones are known as "privileged structures", because they bind to multiple receptor types with high affinity. Toward the development of a novel class of aryldiazepin-2-one scaffolds, the synthesis of pyrrolo[3,2-e][1,4]diazepin-2-ones on a support was explored starting from N-(PhF)-4-hydroxyproline and featuring an acid-catalyzed Pictet-Spengler reaction to form the diazepine ring. Three supports [Wang resin, tetraarylphosphonium (TAP) soluble support, and Merrifield resin] were examined in the synthesis of the heterocycle and exhibited different advantages and disadvantages. Wang resin proved effective for exploratory optimization of the synthesis by identification of intermediates after resin cleavage under mild conditions; however, the acidic conditions of the Pictet-Spengler reaction caused premature loss of resin-bound material. Direct monitoring of reactions by TLC, RP-HPLC-MS, and in certain cases NMR spectroscopy was possible with the TAP support, which facilitated purification of intermediates by precipitation; however, incomplete precipitation of material led to overall yields lower than those from solid-phase approaches on resin. Merrifield resin proved stable to the conditions for the synthesis of the pyrrolo[3,2-e][1,4]diazepin-2-one targets and would be amenable to "split-and-mix" chemistry; however, relatively harsh conditions were necessary for final product cleavage. Perspective for the application of different solid-phase approaches in heterocycle library synthesis was thus obtained by demonstration of the respective utility of the three supports for preparation of pyrrolo[3,2-e][1,4]diazepin-2-one.     

Synthesis of imidazo[4,5-e][1,4]diazepine-8-one

We have developed a method for synthesis of 1-methyl-4,5,7, 8-tetrahydro-6H-imidazo[4,5-e][1,4]diazepin-8-one. We have shown that in intramolecular cyclization of N-(2-hydroxyethyl)- or N-(2-chloroethyl)amides of 1-methyl-4-aminoimidazolyl-5-carboxylic acids it is not the corresponding tetrahydroimidazo[4,5-e][1,4]diazepin-8-ones which are formed but rather the isomeric 4-amino-5-(oxazolin-2-yl)imidazoles.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1203–1206, September, 1993.     

Furo[3,2-e]pyrrolo[1,2-α][1,4]diazepine and derivatives

The 5,10-dihydro-4H-furo[3,2-e]pyrrolo[1,2-α][1,4]diazepin-5-one ( 7 ) and furo[3,2-e]pyrrolo[1,2-α][1,4]diaze-pine ( 10 ) are synthesized from suitable isocyanates 3a,b in acetic acid. The reactivity of 10 (C- and N-alkyla-tion) is investigated.     

2-Pyridylnitrene from tetrazolo[1,5-a]pyridine and pyrido[2,3-a][1,2,4]oxadiazol-2-one

Flash vacuum thermolyses of tetrazolo[1,5- a]pyridine and pyrido[2,3- a][1,2,4]oxadiazol-2-one generate 2-pyridylnitrene, which was detected by Ar matrix ESR spectroscopy. The thermolysis products are 2-aminopyridine, Z- and E-glutacononitriles, and 2- and 3-cyanopyrroles. The products are formed in the same ratios from the two precursors.     

Facile synthesis and antifungal activity of 3-substituted 4-amino-8-ethoxycarbonylpyrazolo[5,1-c][1,2,4]triazines and pyrazolo[1′,5′:3,4][1,2,4]triazino[5,6-b][1,5]benzodiazepines

The reactions of the pyrazole-5-diazonium salt 3 with malononitrile and ethyl cyanoacetate gave 4-amino-3-cyano-8-ethoxycarbonylpyrazolo[5,1-c][1,2,4]triazine 7 and 4-amino-3,8-bisethoxycarbonylpyrazolo[5,1-c]-[1,2,4]triazine 8 , whose reactions with p-chloroaniline hydrochloride afforded 4-amino-8-ethoxycarbonyl-3-(p-chlorophenyl)amidinopyrazolo[5,1-c][1,2,4]triazine 9 and 4-amino-8-ethoxycarbonyl-3-(p-chlorophenyl)car-bamoylpyrazolo[5,1-c][1,2,4]triazine 10 , respectively. The reactions of 7 and 8 with o-phenylenediamine di-hydrochloride provided 9-ethoxycarbonyl-13H-spiro[benzimidazole-2′(3′H),6(5H)-pyrazolo[1,5′:3,4][1,2,4]tri-azino[5,6-b][1,5]benzodiazepine] hydrochloride 11a and 9-ethoxycarbonyl-6-oxo-13H-5,6-dihydropyrazolo-[1′,5′:3,4][1,2,4]triazino[5,6-b][1,5]benzodiazepine 12 , respectively. The antifungal activity of the above compounds was described.     

One-Pot Synthesis of Novel Spiro Pyrano[2,3-d][1,3]thiazolo[3,2-a]pyrimidine Derivatives

In a one-pot synthesis, 1′-methyl-2,3″-dioxo-5″-aryl-1,2,5a″,7″,8″,9a″-hexahydro-5″H,6″H-dispiro[indole-3,2′-pyrrolidine-3′,2″-pyrano[2,3-d][1,3]thiazolo[3,2-a]pyrimidine]-4′-carboxylic acid methyl ester was prepared via the sequential reaction of 4-aryl-octahydro-pyrano[2,3-d]pyrimidine-2-thione, dimethyl acetylenedicarboxylate (DMAD), and a mixture of isatin and sarcosine. All the novel spiro compounds, in moderate yields, were characterized thoroughly by infrared, NMR, mass spectromentry, and elemental analysis together with x-ray crystallographic analysis.     

Synthesis of pyrazolone derivatives—XXI : On the reduction of 1-methyl-2-phenyl-1,2,3,10-tetrahydro-4H-pyrazolo[3,4-c][1] benzothiepin-3,4-dione with sodium borohydride

The selective reduction of α,β-unsaturated ketones and CC double bonds of pyrazolo[3,4-c][1]benzothiepins with sodium borohydride was studied. The reduction of 1-methyl-2-phenyl-1,2,3,10-tetrahydro-4H-pyrazolo[3,4-c][1]benzot (1) with sodium borohydride in refluxing methanol gave 1-methyl-2-phenyl-1,2,3,10-tetrahydro-4H-pyrazolo[3,4-c][1]benzothiepin-3-one (2). The mechanism of this unusual reaction in which the heterocyclic ketone was reduced to the corresponding methylene grouping with such a reagent was elucidated by the isolation of the following intermediates: 1-methyl-2-phenyl-1,2,3,3a, 10, 10a-hexahydro-4H-pyrazolo[3,4-c][1]benzothiepin-3,4-dione (6) and 1-methyl-2-phenyl-1,2,3,3a,10,10a-hexahydro-4H-pyrazolo[3,4-c][1]benzothiepin-3-one (4).