Construction of 6-amino-2,2-dimethyl-3,4,6-trisubstituted-2H-1-benzopyran library by solid phase synthesis

We report the solid-phase library construction of 2000 analogues of 6-amino-2,2-dimethyl-3,4,6-trisubstituted-2H-1-benzopyran. The polymer-bound hydroxyalkoxychromanes 5, produced by nucleophilic reactions with various alcohols on epoxides generated in situ, served as key intermediates for subsequent diversification. Further reactions on these hydroxyalkoxychromanes 5 with various electrophiles, such as alkyl halides and acid halides, produced the desired 6-amino-2,2-dimethyl-3,4,6-trisubstituted-2H-1-benzopyran analogues 9, 10, and 11. The progress of reactions could be monitored as solid-bound intermediates by ATR-FTIR or HR-MAS-NMR spectroscopy. The final compounds, obtained in good yields and high purity upon cleavage from the resins, were characterized by LC/MS, HRMS, (1)H NMR, and (13)C NMR spectroscopy.     

Method for the solid-phase parallel synthesis of a 6-alkylamino-2-(functionalized-aminomethyl)-2H-1-benzopyran Library

A 2000-member library of benzopyran analogues was prepared by using a solid-phase synthesis protocol. Polymer-bound 6-alkylaminobenzopyrans 7 were synthesized as part of a first generation diversification step by employing reactions of a variety of alkyl halides with the amine 6. Transformations of the resin-bound intermediates 8 formed in this manner by reactions with acid halides, sulfonyl chlorides, and isocyanates leads to introduction of the second level of diversification found in the series of 6-alkylamino-2-(functionalized-aminomethyl)-2-methyl-2H-1-benzopyran analogues 11 and 12.     

3,4-二氢-1H-2-苯并吡喃衍生物化合成

3,4-二氢-1 H-2-苯并吡喃也俗称异色满(isochroman)。近年来,将该类化合物引入到药物合成中的研兖引起了人们的兴趣。虽然,已经合成出许多具有镇痛、降血压、抗组胺。和抗肿瘤等药理活性的3,4-二氢-1 H-2-苯并吡喃类化物,合但大都为异色满环上的1,3,4位取代衍生物或者螺环化合物,关于并杂环合成方面的研究至今不多见,作者前     

One-pot rapid synthesis of 4H-1-benzopyran derivatives in a deep eutectic solvent

A method for introducing a biologically active heterocycle, 2-methylquinoline into the 4-position of a 2-amino-4H-1-benzopyran skeleton is described. Choline chloride/glucose (1:1 molar ratio) was used as both the solvent and catalyst in the reaction of a salicylaldehyde, methylquinoline, and cyanoacetate to obtain 2-amino-4H-1-benzopyran derivatives in 48%–80% yields after short reaction times. The effects of the deep eutectic solvent type, substrate molar ratio, cosolvent, temperature, and reaction time were examined. The method has the advantages of simple steps, environmental friendliness, mild conditions, and wide substrate applicability. This is the first attempt to synthesize methylquinoline derivatives of 4H-1-benzopyran.     

Microwave-assisted, solid-phase synthesis of a chiral 1,2,3,4-tetrahydro-quinoline library

The synergy of a solution-phase preparation of scaffolds with a solid-phase combinatorial synthesis let to develop an efficient route to a small library of chiral, highly functionalized tetrahydroisoquinolines. Both loading on the Merrifield resin and the key acid-catalyzed Pictet-Spengler condensation were efficiently promoted by microwave irradiation. The library was designed such that up to five points of diversity would be potentially introduced, making the strategy in principle suitable for generation of a large number of compounds.     

The reactions of 4-dicyanomethylene-2-phenyl-4H-1-benzopyran and some benzologs with nucleophiles

4-Dicyanomethylene-2-phenyl-4H-1-benzopyran (1) reacts with primary amines under mild conditions to give 4-imino-3-alkyl-5-alkylimino-2-phenyl-3,4-dihydro-5H-[1]benzopyrano[3,4-c]-pyridine derivatives which, in turn, are hydrolyzed with acid to 4-imino-3-alkyl-2-phenyl-3,4-dihydro-5H-[1]benzopyrano[3,4-c]pyridin-5-ones. When more vigorous conditions are employed for the reactions of 1 with primary amines, Dimroth rearrangements take place and the products are derivatives of 4-alkyl- (or aryl)amino-5-alkyl- (or aryl)imino-2-phenyl-5H-[1]benzopyrano-[3,4-c]pyridine. The latter compounds are hydrolyzed by acid to the corresponding 5-pyridone derivatives. The reaction of 1 with piperidine gives 2-phenyl-4-piperidyl-5H-[1]benzopyrano-[3,4-c]pyridin-5-one. Sodium methoxide reacts with 1 to give 3-cyano-2-methoxy-4-(2-hydroxyphenyl)-6-phenylpyridine. Two benzologs of 1 have been allowed to react with primary and secondary amines and the products are analogous to those obtained from 1 .     

New synthesis of secondary carboxamide by using 2-methyl-2-oxazoline as a building block

New method for the synthesis of secondary carboxamides of type, R²NHCOR¹, which utilizes 2-methyl-2-oxazoline as a carboxamide building block and various halides, R²X, has been developed.     

Synthesis,structure, and lasing properties of 4-trifluoromethyl-7-hydroxy-2-cyanocarbethoxymethylene-2H-1-benzopyran

Conclusions By condensation of 4-trifluoroacetylresorcinol with cyanoacetic ester, we have obtained 4-trifluoromethyl-7-hydroxy-2-cyanocarbethoxymethylene-2H-1-benzopyran, the structure of which has been proven by an x-ray diffraction investigation. The presence of an elelctron-acceptor group in the 4 position of the benzopyran nucleus leads to a decrease in the degree of charge separation in 2-alkylidenebenzopyrans. We present the lasing characteristics of the compound obtained.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 4, pp. 913–918, April, 1989.     

Regiospecific synthesis of 2-methyl-4-arylcarbonyl-2H-1, 2-benzothiazin-3(4H)-one 1, 1-dioxides

Acylation of 2-methyl-2H-1, 2-benzothiazin-3(4H)-one 1, 1-dioxide 3 with aryl anhydrides in the presence of dimethylaminopyridine occurs regiospecifically to afford 2-methyl-4-arylcarbonyl-2H1, 2-benzothiazin-3(4H)-one 1, 1-dioxides 2a-f .     

Extractive spectrophotometric determination of tungsten(VI) using 3-hydroxy-2-(2'-thienyl)-4-oxo-4H-1-benzopyran

A simple, rapid, highly sensitive and selective spectrophotometric method for the determination of tungsten(VI) in trace amounts is developed using 3-hydroxy-2-(2'-thienyl)-4-oxo-4H-1-benzopyran (HTB) as a reagent for the complexation of metal ion and extracting the 1:2 (metal:ligand) complex into dichloromethane from 0.2 M HCl solution. It obeys Beer's law in the range 0-2.8 microg Wml(-1) with molar absorptivity and Sandell's sensitivity at 415 nm as 6.45 x 10(4) L mol(-1) cm(-1) and 0.0029 microg W(VI) cm(-2), respectively. The method is free from the interference of a large number (39) of elements and handles satisfactorily the analysis of various samples of varying complexity.     

Development of a practical solid-phase synthesis approach to 1,3,5-triazepan-2,6-diones

1,3,5-Triazepan-2,6-diones are a class of conformationally restricted heterocycles derived from dipeptides. With the aim to develop a general and practical method useful for library production, three polymer-assisted syntheses, all based on a catch and release approach, have been evaluated and compared. The method involving a Hofmann rearrangement of N-Boc dipeptide carboxamides and subsequent trapping of the isocyanate on polymer-supported N-hydroxysuccinimide (PS-HOSu) was found to be the most reliable and versatile, allowing rapid access to the 1,3,5-triazepan-2,6-dione skeleton.     

Peptide-heterocycle hybrid molecules: solid-phase synthesis of a 400-member library of N-terminal 2-iminohydantoin peptides

A method for the heterocyclic modification of the N-terminus of a peptide is described. Reaction of the N-terminal amino group of solid-supported peptides with arylisothiocyanates generates a thiourea intermediate, as in the first step of Edman degradation. Treatment of the resin-supported peptide-thioureas with Mukaiyama's reagent (2-chloro-1-methylpyridinium iodide) generates an electrophilic carbodiimide functionality, which undergoes rapid intramolecular trapping by the adjacent amide group to give a 2-iminohydantoin ring at the N-terminus of the peptide. The dehydrothiolation step in the presence of Mukaiyama's reagent prevents Edman degradation from occurring, in essence leading to a "diversion" of the Edman degradation. Cleavage from the resin then releases the hybrid molecules incorporating a 2-iminohydantoin ring conjugated onto a peptidic fragment. A 400-member library of the iminohydantoin-peptide hybrids was synthesized using this approach, starting from a chlorotrityl resin-supported tripeptides.