7 research outputs found
I<sub>2</sub>/Aqueous TBHP-Catalyzed Coupling of Amides with Methylarenes/Aldehydes/Alcohols: Metal-Free Synthesis of Imides
We
present a metal-free method for the synthesis of imides by the
direct coupling of NH-amides with methylarenes under iodine/aqueous
TBHP conditions. The optimized conditions worked very well with benzaldehydes
and benzyl alcohol and furnished the corresponding imides in good
to excellent yields. A series of control and radical scavenger experiments
were also performed, which suggested the involvement of radical pathways.
The labeling experiment in the presence of <sup>18</sup>O-labeled
H<sub>2</sub>O suggested water as a source of oxygen in the imides
Metal-free Cross-Dehydrogenative Coupling of <i>HN</i>-azoles with α‑C(sp<sup>3</sup>)‑H Amides via C–H Activation and Its Mechanistic and Application Studies
A metal-free
one step coupling reaction between various <i>N</i>-azole
rings and diverse α-CÂ(sp<sup>3</sup>)-H containing
amides has been developed under oxidative reaction conditions. Commercially
available tetrabutyl ammonium iodide (TBAI) in the presence of terbutylhydroperoxide
(TBHP), under neat reaction condition, efficiently catalyzed the coupling.
Various azole types, such as 1<i>H</i>-benzotriazoles, 1<i>H</i>-1,2,3-triazoles, 1<i>H</i>-1,2,4-triazoles,
1<i>H</i>-tetrazoles, 1<i>H</i>-pyrazoles, and
1<i>H</i>-benzimidazoles, and α-CÂ(sp<sup>3</sup>)-H
containing amides, such as <i>N</i>,<i>N</i>-dimethylacetamide, <i>N</i>,<i>N</i>-dimethylbenzamide, <i>N</i>-methylacetamide, <i>N</i>,<i>N</i>-diethylacetamide, <i>N</i>-methylpyrrolidine, and pyrrolidine-2-one, were successfully
employed for the coupling. A series of designed and controlled experiments
were also performed in order to study the involvement of the different
intermediates. Based on the evidence, a plausible mechanism is also
proposed. These novel, simple, rapid, attractive, and straightforward
transformations open the way of the construction of novel highly functionalized <i>N</i>-azoles via direct covalent N–H bond transformations
onto N–C bonds. This approach allows to the synthesis of complex
molecules requiring number of steps using classical synthetic ways.
In addition, the range of α-CÂ(sp<sup>3</sup>)-H containing amide
substrates is virtually unlimited highlighting the potential value
of this simple system for the construction of complex heterocyclic
molecules, such as fused azoles derivatives
Metal-free Cross-Dehydrogenative Coupling of <i>HN</i>-azoles with α‑C(sp<sup>3</sup>)‑H Amides via C–H Activation and Its Mechanistic and Application Studies
A metal-free
one step coupling reaction between various <i>N</i>-azole
rings and diverse α-CÂ(sp<sup>3</sup>)-H containing
amides has been developed under oxidative reaction conditions. Commercially
available tetrabutyl ammonium iodide (TBAI) in the presence of terbutylhydroperoxide
(TBHP), under neat reaction condition, efficiently catalyzed the coupling.
Various azole types, such as 1<i>H</i>-benzotriazoles, 1<i>H</i>-1,2,3-triazoles, 1<i>H</i>-1,2,4-triazoles,
1<i>H</i>-tetrazoles, 1<i>H</i>-pyrazoles, and
1<i>H</i>-benzimidazoles, and α-CÂ(sp<sup>3</sup>)-H
containing amides, such as <i>N</i>,<i>N</i>-dimethylacetamide, <i>N</i>,<i>N</i>-dimethylbenzamide, <i>N</i>-methylacetamide, <i>N</i>,<i>N</i>-diethylacetamide, <i>N</i>-methylpyrrolidine, and pyrrolidine-2-one, were successfully
employed for the coupling. A series of designed and controlled experiments
were also performed in order to study the involvement of the different
intermediates. Based on the evidence, a plausible mechanism is also
proposed. These novel, simple, rapid, attractive, and straightforward
transformations open the way of the construction of novel highly functionalized <i>N</i>-azoles via direct covalent N–H bond transformations
onto N–C bonds. This approach allows to the synthesis of complex
molecules requiring number of steps using classical synthetic ways.
In addition, the range of α-CÂ(sp<sup>3</sup>)-H containing amide
substrates is virtually unlimited highlighting the potential value
of this simple system for the construction of complex heterocyclic
molecules, such as fused azoles derivatives
Cross-Dehydrogenative Coupling of Azoles with α‑C(sp<sup>3</sup>)–H of Ethers and Thioethers under Metal-Free Conditions: Functionalization of H–N Azoles via C–H Activation
A metal-free cross-dehydrogenative
coupling method for the synthesis
of <i>N</i>-substituted azoles has been developed. The TBAI/TBHP
system catalyzed the coupling of azoles with ethers and thioethers
via α-CÂ(sp<sup>3</sup>)–H activation. Under the optimized
conditions, a diverse range of un/substituted azoles such as 1<i>H</i>-benzimidazole, 9<i>H</i>-purine, 1<i>H</i>-benzotriazole, 1<i>H</i>-1,2,3-triazole, 1<i>H</i>-1,2,4-triazole, and 1<i>H</i>-pyrazole were successfully
employed for coupling with various ethers and thioethers such as tetrahydrofuran,
tetrahydropyran, 1,4-dioxane, diethyl ether, tetrahydrothiophene,
and 1,3-dithiolane
Metal-free Cross-Dehydrogenative Coupling of <i>HN</i>-azoles with α‑C(sp<sup>3</sup>)‑H Amides via C–H Activation and Its Mechanistic and Application Studies
A metal-free
one step coupling reaction between various <i>N</i>-azole
rings and diverse α-CÂ(sp<sup>3</sup>)-H containing
amides has been developed under oxidative reaction conditions. Commercially
available tetrabutyl ammonium iodide (TBAI) in the presence of terbutylhydroperoxide
(TBHP), under neat reaction condition, efficiently catalyzed the coupling.
Various azole types, such as 1<i>H</i>-benzotriazoles, 1<i>H</i>-1,2,3-triazoles, 1<i>H</i>-1,2,4-triazoles,
1<i>H</i>-tetrazoles, 1<i>H</i>-pyrazoles, and
1<i>H</i>-benzimidazoles, and α-CÂ(sp<sup>3</sup>)-H
containing amides, such as <i>N</i>,<i>N</i>-dimethylacetamide, <i>N</i>,<i>N</i>-dimethylbenzamide, <i>N</i>-methylacetamide, <i>N</i>,<i>N</i>-diethylacetamide, <i>N</i>-methylpyrrolidine, and pyrrolidine-2-one, were successfully
employed for the coupling. A series of designed and controlled experiments
were also performed in order to study the involvement of the different
intermediates. Based on the evidence, a plausible mechanism is also
proposed. These novel, simple, rapid, attractive, and straightforward
transformations open the way of the construction of novel highly functionalized <i>N</i>-azoles via direct covalent N–H bond transformations
onto N–C bonds. This approach allows to the synthesis of complex
molecules requiring number of steps using classical synthetic ways.
In addition, the range of α-CÂ(sp<sup>3</sup>)-H containing amide
substrates is virtually unlimited highlighting the potential value
of this simple system for the construction of complex heterocyclic
molecules, such as fused azoles derivatives
Cross-Dehydrogenative Coupling of Azoles with α‑C(sp<sup>3</sup>)–H of Ethers and Thioethers under Metal-Free Conditions: Functionalization of H–N Azoles via C–H Activation
A metal-free cross-dehydrogenative
coupling method for the synthesis
of <i>N</i>-substituted azoles has been developed. The TBAI/TBHP
system catalyzed the coupling of azoles with ethers and thioethers
via α-CÂ(sp<sup>3</sup>)–H activation. Under the optimized
conditions, a diverse range of un/substituted azoles such as 1<i>H</i>-benzimidazole, 9<i>H</i>-purine, 1<i>H</i>-benzotriazole, 1<i>H</i>-1,2,3-triazole, 1<i>H</i>-1,2,4-triazole, and 1<i>H</i>-pyrazole were successfully
employed for coupling with various ethers and thioethers such as tetrahydrofuran,
tetrahydropyran, 1,4-dioxane, diethyl ether, tetrahydrothiophene,
and 1,3-dithiolane
Design of Novel 3‑Pyrimidinylazaindole CDK2/9 Inhibitors with Potent In Vitro and In Vivo Antitumor Efficacy in a Triple-Negative Breast Cancer Model
In
the present study, a novel series of 3-pyrimidinylazaindoles
were designed and synthesized using a bioinformatics strategy as cyclin-dependent
kinases CDK2 and CDK9 inhibitors, which play critical roles in the
cell cycle control and regulation of cell transcription. The present
approach gives new dimensions to the existing SAR and opens a new
opportunity for the lead optimizations from comparatively inexpensive
starting materials. The study led to the identification of the alternative
lead candidate <b>4ab</b> with a nanomolar potency against CDK2
and CDK9 and potent antiproliferative activities against a panel of
tested tumor cell lines along with a better safety ratio of ∼33
in comparison to reported leads. In addition, the identified lead <b>4ab</b> demonstrated a good solubility and an acceptable in vivo
PK profile. The identified lead <b>4ab</b> showed an in vivo
efficacy in mouse triple-negative breast cancer (TNBC) syngeneic models
with a TGI (tumor growth inhibition) of 90% without any mortality
growth inhibition in comparison to reported leads