332-34-3

Usage

Uses

2,2,2-Trifluoro-n-(4-methoxyphenyl)acetamide is useful in trifluoroacetylation reactions.

InChI:InChI=1/C9H8F3NO2/c1-15-7-4-2-6(3-5-7)13-8(14)9(10,11)12/h2-5H,1H3,(H,13,14)

Upstream product

• 104-94-9 4-methoxy-aniline 
• 407-25-0 trifluoroacetic anhydride 
• 76-05-1 trifluoroacetic acid 
• 2101-87-3 p-methoxy-phenylazide 
• 75999-66-5 N-(4-methoxyphenyl)trifluoroacetimidoyl chloride 
• 104-92-7 1-bromo-4-methoxy-benzene 
• 354-38-1 2,2,2-trifluoroacetamide 
• 696-62-8 para-iodoanisole 
• 464-05-1 pyridinium trifluroacetate 
• 1492828-85-9 methyl 2,2,2-trifluoro-N-(4-methoxyphenyl)acetimidate 
• 383-63-1 ethyl trifluoroacetate, 
• 623-12-1 4-chloromethoxybenzene 
• 354-58-5 1,1,1-Trichloro-2,2,2-trifluoroethane 

Downstream Products

• 2284-20-0 4-Methoxyphenyl isothiocyanate 
• 128691-93-0 4-methoxy-2-nitrotrifluoroacetanilide 
• 1185254-53-8 dimethyl 2-(2,2,2-trifluoro-N-(4-methoxyphenyl)acetamido)-3-(cyclohexylimino)methylene-succinate 
• 1404508-99-1 N-(4-methoxyphenyl)-N-(2,2,2-trifluoroethyl)ethenesulfonamide 
• 79476-73-6 2-((4-methoxyphenyl)amino)acetohydrazide 
• 5421-40-9 N-(4-methoxyphenyl)butyramide 
• 33667-91-3 N-(4-methoxyphenyl)-4-methylbenzamide 
• 32363-18-1 N-(4-methoxyphenyl)-N-methyltrifluoroacetamide 
• 62158-95-6 4-methoxy-N-(2,2,2-trifluoroethyl)aniline 
• 75999-66-5 (Z)-2,2,2-trifluoro-N-(4-methoxyphenyl)acetimidoyl chloride 

Relevant academic research and scientific papers

Direct Synthesis of β-Amino Aldehydes from Linear Allylic Esters Using O2as the Sole Oxidant

A tandem isomerization-anti-Markovnikov oxidation of linear allylic imidic esters is developed using bis(benzonitrile)palladium chloride as the catalyst and O2 as the sole oxidant, regiospecifically giving β-amino aldehydes as the product. tert-Butyl nitrite works as a simple, and the only, redox cocatalyst. tBuOH proves to be a crucial solvent for achieving excellent yield and specificity toward anti-Markovnikov aldehyde products.

ARYL SULFONAMIDES AS SMALL MOLECULE STAT3 INHIBITORS

The present disclosure provides pharmaceutical compositions comprising aryl sulfonamide Stat3 small molecule inhibitors and certain pharmaceutically acceptable salts thereof, and methods of their use for treating cancer.

Novel hybrid conjugates with dual estrogen receptor α degradation and histone deacetylase inhibitory activities for breast cancer therapy

Hormone therapy targeting estrogen receptors is widely used clinically for the treatment of breast cancer, such as tamoxifen, but most of them are partial agonists, which can cause serious side effects after long-term use. The use of selective estrogen receptor down-regulators (SERDs) may be an effective alternative to breast cancer therapy by directly degrading ERα protein to shut down ERα signaling. However, the solely clinically used SERD fulvestrant, is low orally bioavailable and requires intravenous injection, which severely limits its clinical application. On the other hand, double- or multi-target conjugates, which are able to synergize antitumor activity by different pathways, thus may enhance therapeutic effect in comparison with single targeted therapy. In this study, we designed and synthesized a series of novel dual-functional conjugates targeting both ERα degradation and histone deacetylase inhibiton by combining a privileged SERD skeleton 7-oxabicyclo[2.2.1]heptane sulfonamide (OBHSA) with a histone deacetylase inhibitor side chain. We found that substituents on both the sulfonamide nitrogen and phenyl group of OBHSA unit had significant effect on biological activities. Among them, conjugate 16i with N-methyl and naphthyl groups exhibited potent antiproliferative activity against MCF-7 cells, and excellent ERα degradation activity and HDACs inhibitory ability. A further molecular docking study indicated the interaction patterns of these conjugates with ERα, which may provide guidance to design novel SERDs or PROTAC-like SERDs for breast cancer therapy.

Meta Selective C-H Borylation of Sterically Biased and Unbiased Substrates Directed by Electrostatic Interaction

An electrostatically directed meta borylation of sterically biased and unbiased substrates is described. The borylation follows an electrostatic interaction between the partially positive and negative charges between the ligand and substrate. With this strategy, it has been demonstrated that a wide number of challenging substrates, especially 4-substituted substrates, can selectively be borylated at the meta position. Moreover, unsubstituted substrates also displayed excellent meta selectivity. The reaction employs a bench-stable ligand and proceeds at a milder temperature, precluding the need to synthesize a bulky and sophisticated ligand/template.

Electrochemical approach to trifluoroacetamide synthesis from 1,1,1-trichloro-2,2,2-trifluoroethane (CFC-113a) catalyzed by B12complex

One-pot synthetic approach to produce trifluoroacetamide has been developed using an electrochemical method with the B12 complex as a catalyst under mild conditions, in open air at room temperature. Thirty examples of trifluoroacetamide were synthesized from 1,1,1-trichloro-2,2,2-trifluoroethane (CFC-113a) in moderate to good yields. This user-friendly strategy is compatible with a broad range of trifluoroacetamide syntheses.

Exploring the PROTAC degron candidates: OBHSA with different side chains as novel selective estrogen receptor degraders (SERDs)

As the mutant estrogen receptor (ER) continues to be characterized, breast cancer is becoming increasingly difficult to cure when treated with hormone therapy. In this regard, a strategy to selectively and effectively degrade the ER might be an effective alternative to endocrine therapy for breast cancer. In a previous study, we identified a novel series of 7-oxabicyclo[2.2.1]heptene sulfonamide (OBHSA) compounds as full ER antagonists while lacking the prototypical ligand side chain that has been widely used to induce antagonism of ERα. Further crystal structure studies and phenotypic assays revealed that these compounds are selective estrogen receptor degraders (SERDs) with a new mechanism of action. However, from a drug discovery point of view, there still is room to improve the potency of these OBHSA compounds. In this study, we have developed new classes of SERDs that contain the OBHSA core structure and different side chains, e.g., basic side chains, long alkyl acid side chains, and glycerol ether side chains, to simply mimic the degrons of proteolysis targeting chimera (PROTAC) and then investigated the structure-activity relationships of these PROTAC-like hybrid compounds. These novel SERDs could effectively inhibit MCF-7 cell proliferation and demonstrated good ERα degradation efficacy. Among the SERDs, compounds 17d, 17e and 17g containing a basic side chain with a N-trifluoroethyl substituent and a para methoxyl group at the phenyl group of the sulfonamide turned out to be the best candidates for ER degraders. A further docking study of these compounds with ERα elucidates their structure-activity relationships, which provides guidance to design new PROTAC degrons targeting ER for breast cancer therapy. Lastly, easy modification of these PROTAC-like SERDs enables further fine-tuning of their pharmacokinetic properties, including oral availability.

Carbon-Carbon Bond Formation of Trifluoroacetyl Amides with Grignard Reagents via C(O)-CF3 Bond Cleavage

The reaction of trifluoroacetyl amides with Grignard reagent for the substitution of CF3 group with various alkyl or aryl groups is described. A variety of aryl, quinolin-8-yl, and (hetero)alkyl functional groups as well as F, Cl, and Br atoms are well tolerated. These moisture-stable and easily available trifluoroacetyl amides can be conveniently obtained and used as new versatile precursors for isocyanates. The control experiments show that the reaction proceeds via an isocyanate intermediate and/or alkoxide/amide dual anionic intermediate.

Overcoming inaccessibility of fluorinated imines-synthesis of functionalized amines from readily available fluoroacetamides

Although imines are convenient substrates for the synthesis of functionalized amines, they may be hard to obtain, as in the case of fluorinated imines. To aid in overcoming this issue, we propose a protocol of corresponding amine synthesis from simple fluoroacetic acid-derived amides using Schwartz's reagent.

KOtBu-Promoted Transition-Metal-Free Transamidation of Primary and Tertiary Amides with Amines

This work discloses transamidation of primary and tertiary amides with a range of aryl, heteroaryl, and aliphatic amines using potassium tert-butoxide. The reaction proceeds at room temperature under transition-metal-free conditions providing secondary amides in high yields. Moreover, reaction of cyclopropyl amine with tertiary amides proceeds with ring-opening to provide a rapid access to enamides.

Design, Synthesis, and Evaluation of the Highly Selective and Potent G-Protein-Coupled Receptor Kinase 2 (GRK2) Inhibitor for the Potential Treatment of Heart Failure

A novel class of therapeutic drug candidates for heart failure, highly potent and selective GRK2 inhibitors, exhibit potentiation of β-adrenergic signaling in vitro studies. Hydrazone derivative 5 and 1,2,4-triazole derivative 24a were identified as hit compounds by HTS. New scaffold generation and SAR studies of all parts resulted in a 4-methyl-1,2,4-triazole derivative with an N-benzylcarboxamide moiety with highly potent activity toward GRK2 and selectivity over other kinases. In terms of subtype selectivity, these compounds showed enough selectivity against GRK1, 5, 6, and 7 with almost equipotent inhibition to GRK3. Our medicinal chemistry efforts led to the discovery of 115h (GRK2 IC50 = 18 nM), which was obtained the cocrystal structure with human GRK2 and an inhibitor of GRK2 that potentiates β-adrenergic receptor (βAR)-mediated cAMP accumulation and prevents internalization of βARs in β2AR-expressing HEK293 cells treated with isoproterenol. Therefore, 115h appears to be a novel class of therapeutic for heart failure treatment.