Category: nitriles-buliding-blocks

Synthesis and SAR study of potent and selective PI3Kδ inhibitors was written by Bui, Minna;Hao, Xiaolin;Shin, Youngsook;Cardozo, Mario;He, Xiao;Henne, Kirk;Suchomel, Julia;McCarter, John;McGee, Lawrence R.;San Miguel, Tisha;Medina, Julio C.;Mohn, Deanna;Tran, Thuy;Wannberg, Sharon;Wong, Jamie;Wong, Simon;Zalameda, Leeanne;Metz, Daniela;Cushing, Timothy D.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2015.Quality Control of 4-Amino-6-chloropyrimidine-5-carbonitrile This article mentions the following:

2,3,4-Substituted-quinolines such as I were found to be potent inhibitors of PI3Kδ in both biochem. and cellular assays with good selectivity over three other class I PI3K isoforms. Some of those analogs showed favorable pharmacokinetic properties. In the experiment, the researchers used many compounds, for example, 4-Amino-6-chloropyrimidine-5-carbonitrile (cas: 60025-09-4Quality Control of 4-Amino-6-chloropyrimidine-5-carbonitrile).

4-Amino-6-chloropyrimidine-5-carbonitrile (cas: 60025-09-4) belongs to nitriles. Nitrile carbon shifts are in the range of 115–125 ppm whereas in isonitriles the shifts are around 155–165 ppm. Alkyl nitriles are sufficiently acidic to undergo deprotonation of the C-H bond adjacent to the CN group.Strong bases are required, such as lithium diisopropylamide and butyl lithium. The product is referred to as a nitrile anion. Quality Control of 4-Amino-6-chloropyrimidine-5-carbonitrile

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Facile Synthesis of 2-Aminothiophenes Using NaAlO₂ as an Eco-Effective and Recyclable Catalyst was written by Bai, Rongxian;Liu, Ping;Yang, Jian;Liu, Changhui;Gu, Yanlong. And the article was included in ACS Sustainable Chemistry & Engineering in 2015.Product Details of 70291-62-2 This article mentions the following:

Substituted 2-aminothiophenes were synthesized through Gewald reaction by using an easily available solid base catalyst, sodium aluminate. Cost-effectiveness, mild and environmentally benign conditions, and excellent catalytic performance are the features of this system. Furthermore, the NaAlO₂ catalyst can be swimmingly recovered and reused in this reaction. In the experiment, the researchers used many compounds, for example, 2-Amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile (cas: 70291-62-2Product Details of 70291-62-2).

2-Amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile (cas: 70291-62-2) belongs to nitriles. Trimerization of aromatic nitriles requires harsh reaction conditions, high temperatures, long reaction times, and pressure. In conventional organic reductions, nitrile is reduced by treatment with lithium aluminium hydride to the amine. Reduction to the imine followed by hydrolysis to the aldehyde takes place in the Stephen aldehyde synthesis, which uses stannous chloride in acid.Product Details of 70291-62-2

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Discovery, Optimization, and Biological Evaluation of 5-(2-(Trifluoromethyl)phenyl)indazoles as a Novel Class of Transient Receptor Potential A1 (TRPA1) Antagonists was written by Rooney, Lisa;Vidal, Agnes;D’Souza, Anne-Marie;Devereux, Nick;Masick, Brian;Boissel, Valerie;West, Ryan;Head, Victoria;Stringer, Rowan;Lao, Jianmin;Petrus, Matt J.;Patapoutian, Ardem;Nash, Mark;Stoakley, Natalie;Panesar, Moh;Verkuyl, J. Martin;Schumacher, Andrew M.;Petrassi, H. Michael;Tully, David C.. And the article was included in Journal of Medicinal Chemistry in 2014.Category: nitriles-buliding-blocks This article mentions the following:

A high throughput screening campaign identified 5-(2-chlorophenyl)indazole as an antagonist of the transient receptor potential A1 (TRPA1) ion channel with IC₅₀ = 1.23 μM. Hit to lead medicinal chem. optimization established the SAR around the indazole ring system, demonstrating that a trifluoromethyl group at the 2-position of the Ph ring in combination with various substituents at the 6-position of the indazole ring greatly contributed to improvements in vitro activity. Further lead optimization resulted in the identification of compound I, a potent and selective antagonist of TRPA1 in vitro (IC₅₀ = 0.015 μM), which has moderate oral bioavailability in rodents and demonstrates robust activity in vivo in several rodent models of inflammatory pain. In the experiment, the researchers used many compounds, for example, 3-Amino-4-methylbenzonitrile (cas: 60710-80-7Category: nitriles-buliding-blocks).

3-Amino-4-methylbenzonitrile (cas: 60710-80-7) belongs to nitriles. The R-C-N bond angle in and nitrile is 180° which give a nitrile functional group a linear shape. Both the carbon and the nitrogen are sp hydridized which leaves them both with two p orbitals which overlap to form the two π bond in the triple bond. Nitriles are susceptible to hydrogenation over diverse metal catalysts. The reaction can afford either the primary amine (RCH2NH2) or the tertiary amine ((RCH2)3N), depending on conditions.Category: nitriles-buliding-blocks

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

An efficient one-pot synthesis of substituted 2-aminothiophenes via three-component Gewald reaction catalyzed by L-proline was written by Wang, Tao;Huang, Xian-Gui;Liu, Jia;Li, Bo;Wu, Jin-Jin;Chen, Kai-Xian;Zhu, Wei-Liang;Xu, Xiao-Yong;Zeng, Bu-Bing. And the article was included in Synlett in 2010.Synthetic Route of C8H8N2S This article mentions the following:

An efficient one-pot procedure for the direct catalytic synthesis of substituted 2-aminothiophenes catalyzed by L-proline under mild reaction conditions was developed. A variety of functionalized 2-aminothiophene scaffolds were assembled in high yields by this catalytic protocol. Low catalyst loading, simple procedure, and high yields are the important attributes of this methodol. In the experiment, the researchers used many compounds, for example, 2-Amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile (cas: 70291-62-2Synthetic Route of C8H8N2S).

2-Amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile (cas: 70291-62-2) belongs to nitriles. The R-C-N bond angle in and nitrile is 180° which give a nitrile functional group a linear shape. Both the carbon and the nitrogen are sp hydridized which leaves them both with two p orbitals which overlap to form the two π bond in the triple bond. Nitrile groups in organic compounds can undergo a variety of reactions depending on the reactants or conditions. A nitrile group can be hydrolyzed, reduced, or ejected from a molecule as a cyanide ion.Synthetic Route of C8H8N2S

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Synthesis, crystal structures and biological activity of two enantiomeric 2-trifluoromethylthieno[2,3-d]pyrimidin-4-amine derivatives was written by Gao, Hui;Fu, Ju;Zhao, Ming-juan;Song, Xin-jian;Yang, Ping;Zheng, Yin. And the article was included in Chinese Journal of Structural Chemistry in 2015.Recommanded Product: 2-Amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile This article mentions the following:

Two enantiomeric 2-trifluoromethyl-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-amine derivatives were synthesized by nucleophilic substitution of two chiral amines with 4-chloro-2-trifluoromethyl-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidine, which started from 2-amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile, trifluoroacetic acid (TFA) and phosphoryl trichloride via one-pot procedure [I → II; II + (R)/(S)-α-methylbenzylamine → (R)/(S)-III]. Their structures were determined by single-crystal X-ray diffraction. Enantiomer (R)-III, (R)-N-(1-phenylethyl)-2-trifluoromethyl-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-amine crystallizes in the tetragonal system, space group P4₃ with a = 8.6847(6), b = 8.6847(6), c = 22.419(2) Å, V = 1690.9(3) ų, Z = 4, D_c = 1.428 g/cm³, μ = 0.228 mm^-1, F(000) = 752, the final R = 0.0463 and wR = 0.1257 for 3442 observed reflections with I > 2(I). Enantiomer (S)-III, (S)-N-(1-phenylethyl)-2-trifluoromethyl-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-amine crystallizes in the tetragonal system, space group P41 with a = 8.688, b = 8.688, c = 22.421 Å, V = 1692.4 ų, Z = 4, Dc = 1.426 g/cm³, μ = 0.227 mm^-1, F(000) = 752, the final R = 0.0682 and wR = 0.1806 for 3182 observed reflections with I > 2(I). The preliminary bioassay indicated that the R-enantiomer exhibits higher antitumor activity against MCF-7 than gefitinib. In the experiment, the researchers used many compounds, for example, 2-Amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile (cas: 70291-62-2Recommanded Product: 2-Amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile).

2-Amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile (cas: 70291-62-2) belongs to nitriles. Nitriles are polar, as indicated by high dipole moments. As liquids, they have high relative permittivities, often in the 30s. Asymmetric bioreduction of nitriles is an attractive route to produce optically active nitriles as current metal-catalyzed hydrogenations tend to have low reactivity.Recommanded Product: 2-Amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Conversions of carbonyl compounds via their polymeric sulfonylhydrazones into alkenes, alkanes, and nitriles was written by Kamogawa, Hiroyoshi;Kanzawa, Asami;Kadoya, Masahiro;Naito, Takeshi;Nanasawa, Masato. And the article was included in Bulletin of the Chemical Society of Japan in 1983.Name: 2-Cyclohexylacetonitrile This article mentions the following:

RR¹CO [R = H, R¹ = (CH₂)₅Me, Ph, cyclohexyl; R = Me, R¹ = Ph, CH₂CH₂Ph; R = R¹ = Ph, CH₂Ph; RR¹ = (CH₂)₅, (CH₂)₁₁, (CH₂)₂CHMe; RR¹CO = camphor] reacted with hydrazine bound to sulfonated styrene-divinylbenzene copolymer to form polymer-bound sulfonylhydrazones (I). I reacted with alkali to give alkenes, with NaBH₄ or LiAlH₄ to give RCH_iR¹, and with KCN to give RR¹CHCN. The extent of the reaction depended on the type of resin and the bulk of RR¹CO. In the experiment, the researchers used many compounds, for example, 2-Cyclohexylacetonitrile (cas: 4435-14-7Name: 2-Cyclohexylacetonitrile).

2-Cyclohexylacetonitrile (cas: 4435-14-7) belongs to nitriles. Trimerization of aromatic nitriles requires harsh reaction conditions, high temperatures, long reaction times, and pressure. Nitrile groups in organic compounds can undergo a variety of reactions depending on the reactants or conditions. A nitrile group can be hydrolyzed, reduced, or ejected from a molecule as a cyanide ion.Name: 2-Cyclohexylacetonitrile

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

2-(2-Thienyl)-5,6-dihydroxy-4-carboxypyrimidines as Inhibitors of the Hepatitis C Virus NS5B Polymerase: Discovery, SAR, Modeling, and Mutagenesis was written by Koch, Uwe;Attenni, Barbara;Malancona, Savina;Colarusso, Stefania;Conte, Immacolata;Di Filippo, Marcello;Harper, Steven;Pacini, Barbara;Giomini, Claudia;Thomas, Steven;Incitti, Ilario;Tomei, Licia;De Francesco, Raffaele;Altamura, Sergio;Matassa, Victor G.;Narjes, Frank. And the article was included in Journal of Medicinal Chemistry in 2006.Safety of 3-Methylthiophene-2-carbonitrile This article mentions the following:

Infections caused by hepatitis C virus (HCV) are a significant world health problem for which novel therapies are in urgent demand. The polymerase of HCV is responsible for the replication of viral RNA. The authors recently disclosed dihydroxypyrimidine carboxylates as novel, reversible inhibitors of the HCV NS5B polymerase. This series was further developed into 5,6-dihydroxy-2-(2-thienyl)pyrimidine-4-carboxylic acids such as (I) (EC₅₀ 9.3 μM), which now show activity in the cell-based HCV replication assay. The structure-activity relation of these inhibitors is discussed in the context of their physicochem. properties and of the polymerase crystal structure. We also report the results of mutagenesis experiments which support the proposed binding model, which involves pyrophosphate-like chelation of the active site Mg ions. In the experiment, the researchers used many compounds, for example, 3-Methylthiophene-2-carbonitrile (cas: 55406-13-8Safety of 3-Methylthiophene-2-carbonitrile).

3-Methylthiophene-2-carbonitrile (cas: 55406-13-8) belongs to nitriles. The R-C-N bond angle in and nitrile is 180° which give a nitrile functional group a linear shape. Both the carbon and the nitrogen are sp hydridized which leaves them both with two p orbitals which overlap to form the two π bond in the triple bond. Nitriles are susceptible to hydrogenation over diverse metal catalysts. The reaction can afford either the primary amine (RCH2NH2) or the tertiary amine ((RCH2)3N), depending on conditions.Safety of 3-Methylthiophene-2-carbonitrile

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

5,6-Dihydroxypyrimidine Scaffold to Target HIV-1 Nucleocapsid Protein was written by Malancona, Savina;Mori, Mattia;Fezzardi, Paola;Santoriello, Marisabella;Basta, Andreina;Nibbio, Martina;Kovalenko, Lesia;Speziale, Roberto;Battista, Maria Rosaria;Cellucci, Antonella;Gennari, Nadia;Monteagudo, Edith;Di Marco, Annalise;Giannini, Alessia;Sharma, Rajhans;Pires, Manuel;Real, Eleonore;Zazzi, Maurizio;Dasso Lang, Maria Chiara;De Forni, Davide;Saladini, Francesco;Mely, Yves;Summa, Vincenzo;Harper, Steven;Botta, Maurizio. And the article was included in ACS Medicinal Chemistry Letters in 2020.Formula: C7H6N2O This article mentions the following:

The HIV-1 nucleocapsid (NC) protein is a small basic DNA and RNA binding protein that is absolutely necessary for viral replication and thus represents a target of great interest to develop new anti-HIV agents. Moreover, the highly conserved sequence offers the opportunity to escape the drug resistance (DR) that emerged following the highly active antiretroviral therapy (HAART) treatment. On the basis of our previous research, nordihydroguaiaretic acid 1 acts as a NC inhibitor showing moderate antiviral activity and suboptimal drug-like properties due to the presence of the catechol moieties. A bioisosteric catechol replacement approach led us to identify the 5-dihydroxypyrimidine-6-carboxamide substructure as a privileged scaffold of a new class of HIV-1 NC inhibitors. Hit validation efforts led to the identification of optimized analogs, as represented by compound 28, showing improved NC inhibition and antiviral activity as well as good ADME and PK properties. In the experiment, the researchers used many compounds, for example, 4-methoxypicolinonitrile (cas: 36057-44-0Formula: C7H6N2O).

4-methoxypicolinonitrile (cas: 36057-44-0) belongs to nitriles. Nitrile function is a very important functional group because it can be manipulated to other functional groups such as carboxylic acid by hydrolysis or amine by reduction, respectively. Nitrile groups in organic compounds can undergo a variety of reactions depending on the reactants or conditions. A nitrile group can be hydrolyzed, reduced, or ejected from a molecule as a cyanide ion.Formula: C7H6N2O

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

A kinetic study of the N-bromosuccinimide bromination of some 4-substituted 3-cyanotoluenes was written by Fisher, T. H.;Meierhoefer, A. W.. And the article was included in Journal of Organic Chemistry in 1978.Application In Synthesis of 5-Methyl-2-nitrobenzonitrile This article mentions the following:

The log of the relative rates of the N-bromosuccinimide bromination of I (R = H, MeO, PhN₂, Me, Ph, iodo, Br, Cl, F, Ac, CN, NO₂) were linear in σ⁺ with ρ 1.13 ± 0.12. The substituent effects were discussed in terms of polar transition states and bond dissociation energies. The electron withdrawing substituents exhibited extra-resonance in this free radical reaction. In the experiment, the researchers used many compounds, for example, 5-Methyl-2-nitrobenzonitrile (cas: 64113-86-6Application In Synthesis of 5-Methyl-2-nitrobenzonitrile).

5-Methyl-2-nitrobenzonitrile (cas: 64113-86-6) belongs to nitriles. Nitrile function is a very important functional group because it can be manipulated to other functional groups such as carboxylic acid by hydrolysis or amine by reduction, respectively. Some nitriles are manufactured by heating carboxylic acids with ammonia in the presence of catalysts. This process is used to make nitriles from natural fats and oils, the products being used as softening agents in synthetic rubbers, plastics, and textiles and for making amines.Application In Synthesis of 5-Methyl-2-nitrobenzonitrile

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Proton magnetic resonance (NMR) of thiophenes. VIII. Coupling constants in disubstituted thiophenes was written by Hoffman, Ragnar A.;Gronowitz, Salo. And the article was included in Arkiv foer Kemi in 1960.COA of Formula: C5H2N2O2S This article mentions the following:

The ring coupling constants in 19 2,5-, 17 2,3-, 18 2,4-, and 11 3,4-disubstituted thiophenes are reported. The values are: J₃₄ = 3.45-4.35; J₄₅ = 4.90-5.80; J₃₅ = 1.25-1.70; and J₂₅ = 3.20-3.65 cycles/sec., all values ±0.15 cycles/sec. These values were compared with the spin couplings of other monocyclic aromatic systems. Couplings between the side-chain proton and ring protons were observed in methylthiophenes, thiophene aldehydes, and thiophene thiols. These side-chain couplings have values of J_CH3-3 = 1.00-1.15, J_CH3-4 = 0.2-0.5 and J_CH3-5 <0.4 in 2-methylthiophenes; J_CH3-2= 0.9-1.25, J_CH34 ≈ J_CH3-5 =0.4-0.5 in 3-methylthiophenes; J_CHO-5 = 1.05-1.40 in 2-thiophenealdehydes; J_CHO-5 = (<0.4)-0.80 in 3-thiophenealdehydes; J_SH-3 = 1.4-1.60, J_SH-5= 0.90-1.0 in 2-thiophenethiols; J_SH-2 = 0.65-1.05, J_SH-5 ≤ 0.3 cycles/sec. in 3-thiophenethiols. Couplings between protons of different side-chains were observed in the 3- and 5-methyl-2-thiophenethiols and in 2-methyl-3-thiophenethiol, but not in 3-methyl-4-thiophenethiol or any methyl-substituted thiophene aldehyde. An explanation for these observations isproposed. In the experiment, the researchers used many compounds, for example, 4-Nitrothiophene-2-carbonitrile (cas: 42137-24-6COA of Formula: C5H2N2O2S).

4-Nitrothiophene-2-carbonitrile (cas: 42137-24-6) belongs to nitriles. The R-C-N bond angle in and nitrile is 180° which give a nitrile functional group a linear shape. Both the carbon and the nitrogen are sp hydridized which leaves them both with two p orbitals which overlap to form the two π bond in the triple bond. Alkyl nitriles are sufficiently acidic to undergo deprotonation of the C-H bond adjacent to the CN group.Strong bases are required, such as lithium diisopropylamide and butyl lithium. The product is referred to as a nitrile anion. COA of Formula: C5H2N2O2S

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts