Asymmetric 1,3-Dipolar Cycloaddition Reactions

Chem. Pharm. Bull.(オピニオン)

Recent developments in the chemistry of enaminones

Synthesis of heterocycles from alkyl 3-(dimethylamino)propenoates and related enaminones.

Compounds, pharmaceuticals, kits and methods are provided for use with DPP-IV and other S9 proteases that comprise a compound comprising: 
wherein M is N or CR 4 ; Q 1 and Q 2 are each independently selected from the group consisting of CO, SO, SO 2 , and C═NR 9 ; and each L, X, R 1 , R 2 , and R 3 are as defined herein.

Dipeptidyl peptidase inhibitors

The synthesis of ethyl 2-(2-acetyl-2-benzoyl-1-ethenyl)amino-3-dimethylarninopropenoate (4) from benzoylacetone (1) via 3-dimethylarninomethylenebenzoylacetone (2) and ethyl N-(2-acetyl-2-benzoyl-1-ethenyl)glycinate (3) and its transformation into 4-benzoyl-2-ethoxycarbonyl-3-methylpyrrole (9) is described. Cyclization of 4 into 9 represents a new synthesis of polysubstituted pyrroles.

The Synthesis and Transformation of Ethyl 2‐(2‐Acetyl‐2‐benzoyl‐1‐ethenyl)amino‐3‐dimethylaminopropenoate. A New Synthesis of 2,3,4‐Trisubstituted Pyrroles.

Reactions of cyclic enaminones, derived from cyclic five- and six-membered 1,3-diones, and dimethyl acetylenedicarboxylate (DMAD) under microwave irradiation produced a mixture of two products: ring-expansion products as a result of a [2+2] cycloaddition and Michael adducts. Reaction between 4-(dimethylamino)-2H-chromen-2-one and DMAD leads to three products: 2-(4-(dimethylamino)-2-oxo-2H-chromen-3-yl)maleate as a Michael adduct, dimethyl 1-(dimethylamino)naphthalene-2,3-dicarboxylate as the product of the [2+2] cycloaddition followed by 6π disrotatory electrocyclization and elimination of CO2 and 4-(dimethylamino)naphthalene-1,2-dicarboxylate as the product of the [4+2] cycloaddition followed by elimination of CO2.

[2 + 2] Cycloadditions of Electron-Poor Acetylenes to Endocyclic Enaminones: Ring-Expansion Reactions.

6-Methoxy-2-methylpyridazin-3(2H)-one (1) gave with 2-diazopropane (8) a mixture of 3H-pyrazolo[3,4-d]-pyridazin-4(5H)-one derivative 12, as the main product, and -7(6H)-one derivative 10, as the minor product. On the other hand, 4-substituted pyridazin-3(2H)-ones 2, 3, and 4 gave 3H-pyrazolo[3,4-d]pyridazin-7(6H)-one 10, exclusively, while 5-substituted pyridazin-3(2H)-ones 5, 6, and 7 produced only the isomeric 3H-pyrazolo[3,4-H]pyridazin-4(5H)-one 12. The 5-phenylsulfonyl derivative 13 gave with 8 by elimination of a molecule of nitrogen, followed by rearrangement, 1,2-diazepine derivative 15 and with an excess of 8 3H-pyrazolo[3,4-d][1,2]diazepine derivative 16. 1,2-Dimethylpyridazine-3,6-(1H,2H)-dione and its derivatives 18 and 19 produced 3H-pyrazolo[3,4-d]pyridazine-4,7(5H,6H)-dione derivative 23, while from 17 and 1-diazoindane (24) the spiro compound 27 was obtained. The 1,2-dihydro and 3a,7a-dihydro intermediates 21 and 25 were isolated.

Directed Regiospecificity of 1,3‐Dipolar Cycloaddition of 2‐ Diazopropane to 4‐ and 5‐Substituted Pyridazin‐3(2H)‐ones.

Transformations of intermediates 4, prepared from methyl 2-(2,2-disubstituted-ethenyl)amino-3-dimethylaminopropenoates 2 and sterically hindered heteroarylamines 3, into methyl 1-heteroaryl-1H-imidazole-4-carboxylates 7 are described.

Transformations of Methyl 2-(2,2-Disubstituted-ethenyl)amino-3-dimethylaminopropenoates. The Synthesis of Methyl 1-Heteroaryl-1H-imidazole-4-carboxylates.

Alkyl (E,Z)-2-(2-benzoyl-2-ethoxycarbonyl-1-ethenyl)amino-3-dimethylaminopropenoates 1a,b react with het-eroarylamines 2 to give alkyl 2-(2-benzoyl-2-ethoxycarbonyl-1-ethenyl)amino-3-heteroarylaminopropenoates 3-13. These were cyclized into fused 3-(2-benzoyl-2-ethoxycarbonyl-1-ethenyl)amino-4H-azolo- (or azino)-pyrim-idin-4-ones 14-18. 2-Benzoyl-2-ethoxycarbonyl-1-ethenyl group can be easily removed from 3-(2-benzoyl-2-ethoxycarbonyl-1-emenyl)amino-8-memyl-4H-pyrido[1,2-a]pyrimidin-4-one (14) to give 3-amino-8-methyl-4H-pyrido[1,2-a]pyrimidin-4-one (19). The structure of 1a was confirmed by X-ray analysis.

Alkyl (E,Z)-2-(2-Benzoyl-2-ethoxycarbonyl-1-ethenyl) amino-3-dimethylaminopropenoates in the Synthesis of Fused Pyrimidinones. A Facile Route to 3-Aminoazino-4H-pyrimidin-4-ones.

Branko Stanovnik

Papers

The Synthesis and Transformation of Ethyl 2‐(2‐Acetyl‐2‐benzoyl‐1‐ethenyl)amino‐3‐dimethylaminopropenoate. A New Synthesis of 2,3,4‐Trisubstituted Pyrroles.

[2 + 2] Cycloadditions of Electron-Poor Acetylenes to Endocyclic Enaminones: Ring-Expansion Reactions.

Directed Regiospecificity of 1,3‐Dipolar Cycloaddition of 2‐ Diazopropane to 4‐ and 5‐Substituted Pyridazin‐3(2H)‐ones.

Transformations of Methyl 2-(2,2-Disubstituted-ethenyl)amino-3-dimethylaminopropenoates. The Synthesis of Methyl 1-Heteroaryl-1H-imidazole-4-carboxylates.

Alkyl (E,Z)-2-(2-Benzoyl-2-ethoxycarbonyl-1-ethenyl) amino-3-dimethylaminopropenoates in the Synthesis of Fused Pyrimidinones. A Facile Route to 3-Aminoazino-4H-pyrimidin-4-ones.