5515-16-2

Usage

Physical state

Colorless liquid

Solubility

Insoluble in water

Reactivity

Highly reactive

Uses

Organic synthesis (Michael acceptor), production of pharmaceuticals and agrochemicals, precursor in the synthesis of various compounds (including pharmaceutical intermediates)

Reaction types

Michael addition, Knoevenagel condensation, cyanoethylation

Applications

Development of new materials, building block for the synthesis of complex molecules.

Upstream product

• 186581-53-3 diazomethane 
• 5515-35-5 2-(1-hydroxy-ethylidene)malononitrile 
• 672-81-1 2-(methoxymethylene)malononitrile 
• 67-56-1 methanol 
• 93102-10-4 dicyano-1,1 propadiene 
• 78-39-7 Triethyl orthoacetate 
• 109-77-3 malononitrile 
• 1445-45-0 Trimethyl orthoacetate 
• 616-42-2 dimethylsulfite 
• 1187-11-7 acetylmalonodinitrile 
• 149-73-5 trimethyl orthoformate 
• 93102-15-9 bis-(cyano) methylene-11 ethano-9,10 dihydro-9,10 anthracene 

Downstream Products

• 108675-18-9 2-Cyan-3-<(benzyliminomethyl-λ⁶-sulfanyliden)amino>-3-methylacrylnitril 
• 108675-19-0 2-Cyan-3-<(dibenzylimino-λ⁶-sulfanyliden)amino>-3-methylacrylnitril 
• 107325-87-1 2-<1-(1-Methyl-5-phenyl-1λ⁴,4-thiazin-3-ylamino)ethyliden>malononitril-S-oxid 
• 107325-88-2 2-<1-(1-Methyl-5-p-tolyl-1λ⁴,4-thiazin-3-ylamino)ethyliden>malononitril-S-oxid 
• 107325-89-3 2-<1-<5-(4-Clorphenyl)-1-methyl-1λ⁴,4-thiazin-3-ylamino>ethyliden>malononitril-S-oxid 
• 107325-93-9 8-Amino-1,6-dimethyl-3-phenylpyrido<3,2-b>-1λ⁴,4-thiazin-7-carbonitril-1-oxid 
• 107325-94-0 8-Amino-1,6-dimethyl-3-p-tolylpyrido<3,2-b>-1λ⁴,4-thiazin-7-carbonitril-1-oxid 
• 107325-95-1 8-Amino-3-(4-chlorphenyl)-1,6-dimethylpyrido<3,2-b>-1λ⁴,4-thiazin-7-carbonitril-1-oxid 
• 104366-22-5 2-amino-4-methoxythiophene-3-carbonitrile 
• 21642-98-8 2-hydroxy-4-methoxypyridine-3-carbonitrile 
• 95689-38-6 1,1-dicyano-4-(N,N-dimethylamino)-2-methoxy-1,3-butadiene 
• 87412-84-8 4-amino-3-methyl-1-phenylpyrazolo<3,4-d>pyrimidine 
• 5346-58-7 4-amino-1,3-dimethyl-1H-pyrazolo<3,4-d>pyrimidine 
• 5399-44-0 3-methyl-4-amino-1H-pyrazolo[3,4-d]pyrimidine 

Relevant academic research and scientific papers

3-cyanopyrazolopyrimidine [1,5-a] derivative as well as preparation method and application thereof

The invention belongs to the field of chemical medicines and specifically relates to a 3-cyanopyrazolopyrimidine [1,5-a] derivative as well as a preparation method and application thereof. The invention provides the 3-cyanopyrazolopyrimidine [1,5-a] derivative, and the structure of the 3-cyanopyrazolopyrimidine [1,5-a] derivative is shown as a formula I. The invention further provides the preparation method and the application of the 3-cyanopyrazolopyrimidine [1,5-a] derivative. (The formula I is shown in the description).

1,3-disubstituted-4-aminopyrazolo [3, 4-d] pyrimidines, a new class of potent inhibitors for phospholipase D

Phospholipase D enzymes cleave lipid substrates to produce phosphatidic acid, an important precursor for many essential cellular molecules. Phospholipase D is a target to modulate cancer-cell invasiveness. This study reports synthesis of a new class of phospholipase D inhibitors based on 1,3-disubstituted-4-amino-pyrazolopyrimidine core structure. These molecules were synthesized and used to perform initial screening for the inhibition of purified bacterial phospholipase D, which is highly homologous to the human PLD1. Initially tested with the bacterial phospholipase D enzyme, then confirmed with the recombinant human PLD1 and PLD2 enzymes, the molecules presented here exhibited inhibition of phospholipase D activity (IC50) in the low-nanomolar to low-micromolar range with both monomeric substrate diC4PC and phospholipid vesicles and micelles. The data strongly indicate that these inhibitory molecules directly block enzyme/vesicle substrate binding. Preliminary activity studies using recombinant human phospholipase Ds in in vivo cell assays measuring both transphosphatidylation and head-group cleavage indicate inhibition in the mid- to low-nanomolar range for these potent inhibitory novel molecules in a physiological environment. This study reports synthesis of a new class of PLD inhibitors based on 1,3-disubstituted-4-amino-pyrazolopyrimidine core structure. These molecules exhibited inhibition of human recombinant PLD activity (IC 50) in the low-nanomolar to low-micromolar range with monomeric substrate diC4PC and phospholipid vesicles and micelles. Preliminary activity studies using recombinant human PLDs in in vivo cell assays measuring both transphosphatidylation and head-group cleavage indicates inhibition in the mid- to low-nanomolar range for these potent inhibitory novel molecules in a physiological environment.

BICYCLIC HETEROCYCLES AS FGFR INHIBITORS

The present invention relates to bicyclic heterocycles, and pharmaceutical compositions of the same, that are inhibitors of one or more FGFR enzymes and are useful in the treatment of FGFR-associated diseases such as cancer.

Transesterification of trimethyl orthoacetate: An efficient protocol for the synthesis of 4-alkoxy-2-aminothiophene-3-carbonitriles

A facile one-pot method is reported for the synthesis of 4-alkoxy-2-aminothiophene-3-carbonitriles. Transesterification of trimethylorthoacetate technique allowed introducing alkoxy substituents into 2-aminothiophene ring system. Diverse alkoxy substituents could be introduced efficiently by using this methodology. Further the synthesis of some of new 4-alkylamino-2-aminothiophenes is also reported.

Fragment-based design, synthesis, and biological evaluation of N-substituted-5-(4-isopropylthiophenol)-2-hydroxynicotinamide derivatives as novel Mcl-1 inhibitors

We have previously reported a nanomolar inhibitor of antiapoptotic Mcl-1 protein, 3-thiomorpholin-8-oxo-8H-acenaphtho [1,2-b] pyrrole-9-carbonitrile (S1). S1 plays its function by binding to the BH3 groove of Mcl-1. Basing on this spacial structural characteristic, we developed a novel class of Mcl-1 inhibitor using fragment-based drug discovery approach. By dissecting S1, we identified the compound 4 with a 2-hydroxypyridine core as the starting fragment. In the following molecular growth, we used the ligand efficiency evaluation and fit quality score to assess the fragments. A novel potent compound, N-benzyl-5-(4-isopropylthiophenol)-2-hydroxyl nicotinamide (12c), which binds Mcl-1 with an IC50 value of 54 nM was obtained. Compound 12c demonstrated a better aqueous solubility than S1.

CHEMICAL COMPOUNDS

The invention is directed to pyrido[4,3-d]pyrimidin-5(6H)-one derivatives. Specifically, the invention is directed to compounds according to Formula (I) wherein R1, R2, R3, and R4 are defined below. The compound

NOVEL HETEROCYCLES

Described are novel heterocyclic compounds of the general formula (I), their derivatives, analogs, tautomeric forms, stereoisomers, polymorphs, hydrates, solvates, pharmaceutically acceptable salts, pharmaceutical compositions, metabolites and prodrugs th

Novel heterocycles

The present invention relates to novel heterocyclic compounds of the general formula (I), their derivatives, analogs, tautomeric forms, stereoisomers, polymorphs, hydrates, solvates, pharmaceutically acceptable salts and compositions, metabolites and prod

Solvent Effect on Product Distribution in the Thermolysis of Dihydropyrazoles

Solvent dependence of products in the thermal decomposition of 4-methoxy-4,5-dihydro-3H-pyrazoles bearing two electronegative groups at C-3 was observed; nonpolar solvent gave predominantly alkenes, whereas polar solvents gave predominantly cyclopropanes.

Reactions retrodieniques - XVIII. Synthese par thermolyse eclair et etude d'allenes fonctionnels reactifs

The flash thermolysis of anthracenic Diels-Alder adducts leads to the obtention and low temperature spectroscopic characterization (ir, 1H and 13C nmr) of allenes 1-11 (see table 1).Butadienal 1, the simplest α-allenic aldehyde, is thus obtained from its precursors 13, 14 or 17.Thermolysis of the intermediate allylic alcohol 15 gives buta-1,3-dien-2-ol 18, which tautomerizes to methylvinylketone even at -100 deg C.An attempted synthesis of a natural δ-allenic ester, methyl laballenate 19, was undertaken using this method; however, the thermolysis of ester 24 leads via 19 to methyl acrylate and (Z + E) pentadeca-1,3-diene 25, resulting formally from a retroene cleavage of 19.Thermolyses of related esters 26 and 27 give in the same way the corresponding 1,3-dienes.Allenes with gem electron attracting groups are very reactive compounds acting as ketene equivalents in nucleophilic additions and or dipolar cycloadditions.The thermolysis of adducts 28-32, obtained by Knoevenagel condensation of malonic derivatives with ketone 16, leads to the following allenes of this series: 1,1-dicyano-1-methoxycarbonyl propadiene 4, 1,1-bis-(ethoxycarbonyl) propadiene 5 and 1,1-bis-(methoxycarbonyl) propadiene 6.Yields and purity are lower in the case of 3 and 5, owing to the presence of the thermolabile ethoxycarbonyl groups.The possibility of performing nucleophilic additions to the most polymerizable of these allenes: 1,1-dicyanopropadiene 2, is demonstrated by its clean, good yield additions at -50 deg C with methanol, methyl lithium, aniline ir dimethylamine.Allenes O or N-substituted on the allenic carbon are often reactive substances and are known mainly in the case of alkyl ethers and tertiary amines.The flash thermolysis of allylic alcohol 38 gives in good yield propanediol 7 which tautomerizes into acrolein at -50 deg C.Trimethylsilyloxypropadiene 8, 1-trimethylsilyloxybuta-1,2-diene 9 and 3-trimethylsilyloxybuta-1,2-diene 10 could also be obtained from their precursors 40, 44-46.Thermolysis of amine 49 leads in the same way to propadienamine 11, a reactive enamine postulated as a cosmic species and tautomerizing at -65 deg C into 1-azabuta-1,3-diene 50.