404-25-1

Basic information

• Product Name: AcetaMide, N-(4-chlorophenyl)-2,2,2-trifluoro-
• Synonyms: AcetaMide, N-(4-chlorophenyl)-2,2,2-trifluoro-
• CAS NO: 404-25-1
• Molecular Formula: C₈H₅ClF₃NO
• Molecular Weight: 223.5796096
• Mol File: 404-25-1.mol

Chemical Properties

• Boiling Point: 276.4°Cat760mmHg
• Flash Point: 121°C
• Appearance: /
• Density: 1.482g/cm³
• Vapor Pressure: 0.00481mmHg at 25°C
• Refractive Index: 1.52
• CAS DataBase Reference: AcetaMide, N-(4-chlorophenyl)-2,2,2-trifluoro-(CAS DataBase Reference)
• NIST Chemistry Reference: AcetaMide, N-(4-chlorophenyl)-2,2,2-trifluoro-(404-25-1)
• EPA Substance Registry System: AcetaMide, N-(4-chlorophenyl)-2,2,2-trifluoro-(404-25-1)

Safety Data

• Hazardous Substances Data: 404-25-1(Hazardous Substances Data)

Usage

InChI:InChI=1/C8H5ClF3NO/c9-5-1-3-6(4-2-5)13-7(14)8(10,11)12/h1-4H,(H,13,14)

Upstream product

• 13081-18-0 ethyl-3,3,3-trifluoropyruvate 
• 106-47-8 4-chloro-aniline 
• 1492828-77-9 methyl 2,2,2-trifluoro-N-(p-chlorophenyl)acetimidate 
• 143681-32-7 N-(4-chlorophenyl)-2,2,2-trifluoroethanimidoyl chloride 
• 2923-18-4 sodium 2,2,2-trifluoroacetate 
• 407-25-0 trifluoroacetic anhydride 
• 953-14-0 N,N'-bis(4-chlorophenyl)hydrazine 

Downstream Products

• 1404509-02-9 N-(4-chlorophenyl)-N-(2,2,2-trifluoroethyl)ethenesulfonamide 
• 33667-89-9 N-(4-chlorophenyl)-4-methylbenzamide 
• 2371-31-5 2-((4-chlorophenyl)amino)acetohydrazide 
• 144181-67-9 N-(4-chloro-2-hydroxyphenyl)-2,2,2-trifluoroacetamide 
• 1374845-73-4 FeCu(C₅H₄P(C₆H₅)2)2NCOCF₃C₆H₄Cl 
• 143681-32-7 (1Z)-N-(4-chlorophenyl)-2,2,2-trifluoroethanimidoyl chloride 
• 128691-94-1 N-(2-Amino-4-chloro-phenyl)-2,2,2-trifluoro-acetamide 
• 22753-82-8 4-chloro-N-(2,2,2-trifluoroethyl)benzenamine 
• 2131-55-7 4-Chlorophenyl isothiocyanate 

Relevant articles and documents

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.

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.

Synthetic method of trifluoroacetanilide derivative

The invention belongs to the technical field of organic synthetic intermediate, and more specifically relates to a method used for catalytic synthesis of a trifluoroacetanilide derivative under catalytic effect of copper. The method comprises following steps: 1, dimethyl sulfoxide, an aniline derivative, ethyl trifluoropyruvate, and cuprous chloride are delivered into a pressure-resistant reaction tube, the pressure-resistant reaction tube is sealed with a plug, and reaction is carried out for 12h in oil bath at 80 DEG C with magnetic stirring; 2, after reaction, extraction is carried out with ether, obtained organic phase substances are mixed, and reduced pressure distillation is carried out so as to remove most of the solvents, and an obtained mixed solution is subjected to column chromatography separation purification with an eluent composed of petroleum ether and ethyl acetate at a volume ratio of 2:1-10:1 so as to obtain a finished product. The trifluoroacetanilide derivative can be widely used in the fields such as organic synthesis, medicine industry, and pesticide industry; cost is low; operation is simple; the substances are widely available; yield is high; and application prospect is promising.

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.

Removal of some common glycosylation by-products during reaction work-up

With the aim of improving the general glycosylation protocol to facilitate easy product isolation it was shown that amide by-products from glycosylation with trichloroacetimidate and N-phenyl trifluoroacetimidate donors could be removed during reaction work-up by washing with a basic aqueous solution. Excess glycosyl acceptor or lactol originating from glycosyl donor hydrolysis could equally be removed from the reaction mixture by derivatization with a basic tag and washing with an acidic solution during reaction work-up.

Catalytic reduction of amides to amines by electrophilic phosphonium cations via FLP hydrosilylation

A catalytic methodology for the conversion of amides to amines is reported. Of the 25 examples described, 14 examples involve the reduction of N-trifluoroacetamides to the corresponding trifluoroethylamines. These reductions are achieved by catalytic hydrosilylation of the amide mediated by an electrophilic phosphonium cation (EPC) catalyst.

The development of N-aryl trifluoroacetimidate-based benzyl and allyl protecting group reagents

An exploration of the role of para-substituents on the balance between stability and reactivity of N-phenyl trifluoroacetimidates prompted the discovery of new reagents for the addition of allyl and benzyl protecting groups, namely O-allyl and O-benzyl N-

Bicyclic core estrogens as full antagonists: Synthesis, biological evaluation and structure-activity relationships of estrogen receptor ligands based on bridged oxabicyclic core arylsulfonamides

Compounds that block estrogen action through the estrogen receptor (ER) or downregulate ER levels are useful for the treatment of breast cancer and endocrine disorders. In our search for structurally novel estrogens having three-dimensional core scaffolds, we found some compounds with a 7-oxabicyclo[2.2.1]heptene core that bound well to the ERs. The best of these compounds, a phenyl sulfonate ester (termed OBHS for oxabicycloheptene sulfonate), was a partial antagonist on both ERα and ERβ. Although OBHS bears no structural resemblance to other estrogen antagonists, it appears to achieve its partial antagonist character by stabilizing a novel conformation of the ER that involves a significant distortion of helix-11. To enhance the antagonist properties of these oxabicyclo[2.2.1]heptane core ligands, we expanded the functional diversity of OBHS by replacing the sulfonate with secondary or tertiary sulfonamides (-SO2NR-), isoelectronic and potentially isostructural molecular replacements. An array of 16 OBHS sulfonamide analogues were prepared through a Diels-Alder reaction of a 3,4-diarylfuran using various N-aryl vinyl sulfonamide dienophiles. While the more polar secondary sulphonamides were weak ligands, certain of the tertiary sulfonamides had very good ER binding affinity. In HepG2 cell reporter gene assays, the sulphonamides had moderate potency, but they showed lower intrinsic transcriptional activity on ERα than the selective estrogen receptor modulator (SERM) hydroxytamoxifen or OBHS, and they were inverse agonists on ERβ. Thus, the behaviour of these OBH-sulfonamides more closely mirrors the activity of full antagonists like the drug fulvestrant (ICI 182780), and their greater antagonist biocharacter appears to arise from an accentuated distortion of helix-11.

ANTAGONISTS OF MELANIN CONCENTRATING HORMONE RECEPTOR

This invention provides compounds that are antagonists of melanin concentrating hormone receptor-1 (MCH-R1). The compounds are represented by formula (I): where m is zero or one, n is zero to two, Y is oxygen or -N (R9)-, R1, R2, R3, R4, R5, R9, and Ring A are defined in the specification. Coumarin and quinolone compounds where R1 and R2 together form a fused benzo ring are preferred. The invention also provides compounds of formula (VI) where the coumarin moiety is replaced by a quinazolinone ring. The compounds are useful for treating MCH-R1-related disorders, particularly overweight conditions including obesity.