22753-82-8

Upstream product

• 404-25-1 N-(4-chlorophenyl)-2,2,2-trifluoroacetamide 
• 1241540-08-8 4-chloro-N-(2,2,2-trifluoro-1-methoxyethyl)aniline 
• 637-87-6 1-Chloro-4-iodobenzene 
• 753-90-2 trifluoroethylamine 
• 373-88-6 2,2,2-trifluroethylamine hydrochloride 
• 106-47-8 4-chloro-aniline 
• 371-67-5 2,2,2-trifluorodiazoethane 
• 23199-56-6 2,2,2-trifluoroethyltrichloromethanesulfonate 

Downstream Products

• 34483-02-8 N¹-(4-Chloro-phenyl)-N¹-(2,2,2-trifluoro-ethyl)-ethane-1,2-diamine 
• 1404509-02-9 N-(4-chlorophenyl)-N-(2,2,2-trifluoroethyl)ethenesulfonamide 
• 638191-87-4 N-(4-chlorophenyl)-N-(2,2,2-trifluoroethyl)malonamic acid t-butyl ester 

Relevant academic research and scientific papers

Iron porphyrin-catalyzedN-trifluoroethylation of anilines with 2,2,2-trifluoroethylamine hydrochloride in aqueous solution

An iron porphyrin-catalyzedN-trifluoroethylation of anilines has been developed with 2,2,2-trifluoroethylamine hydrochloride as the fluorine source. This one-pot N-H insertion reaction is conductedviacascade diazotization/N-trifluoroethylation reactions.

B(C6F5)3-Catalyzed Deoxygenative Reduction of Amides to Amines with Ammonia Borane

The first B(C6F5)3-catalyzed deoxygenative reduction of amides into the corresponding amines with readily accessible and stable ammonia borane (AB) as a reducing agent under mild reaction conditions is reported. This metal-free protocol provides facile access to a wide range of structurally diverse amine products in good to excellent yields, and various functional groups including those that are reduction-sensitive were well tolerated. This new method is also applicable to chiral amide substrates without erosion of the enantiomeric purity. The role of BF3 ? OEt2 co-catalyst in this reaction is to activate the amide carbonyl group via the in situ formation of an amide-boron adduct. (Figure presented.).

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.

Method of catalyzing trifluoro-ethylation of aromatic primary amine by ferriporphyrin

The invention provides a method of catalyzing trifluoro-ethylation of aromatic primary amine by ferriporphyrin. The method comprises the following steps: adding trifluoroethylamine salt and nitrite toa diazo-reaction first and then adding aromatic primary

Highly Chemoselective Iridium Photoredox and Nickel Catalysis for the Cross-Coupling of Primary Aryl Amines with Aryl Halides

A visible-light-promoted iridium photoredox and nickel dual-catalyzed cross-coupling procedure for the formation C?N bonds has been developed. With this method, various aryl amines were chemoselectively cross-coupled with electronically and sterically diverse aryl iodides and bromides to forge the corresponding C?N bonds, which are of high interest to the pharmaceutical industries. Aryl iodides were found to be a more efficient electrophilic coupling partner. The coupling reactions were carried out at room temperature without the rigorous exclusion of molecular oxygen, thus making this newly developed Ir-photoredox/Ni dual-catalyzed procedure very mild and operationally simple.

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.

Silver(I)-Catalyzed N-Trifluoroethylation of Anilines and O-Trifluoroethylation of Amides with 2,2,2-Trifluorodiazoethane

A straightforward N-trifluoroethylation of anilines has been developed based on silver-catalyzed N￡H insertions with 2,2,2-trifluorodiazoethane (CF3CHN2). Mechanistically, the reaction is proposed to involve migratory insertion of a silver carbene as the key step. In contrast, when amides are employed as the substrates under similar reaction conditions, O-trifluoroethylation occurs to afford trifluoroethyl imidates.

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.

Trifluoroacetaldehyde: A useful industrial bulk material for the synthesis of trifluoromethylated amino compounds

The synthesis of various trifluoromethylated amino compounds was studied using trifluoroacetaldehyde, an industrial bulk material, as a starting compound. One general application of trifluoroacetaldehyde is the preparation of trifluoroethylamino derivatives via reductive amination reaction. This synthesis includes the formation of the corresponding N,O-acetal intermediates followed by their reduction using NaBH4 or 2-picoline borane complex, affording the target trifluoroethylamino compounds in moderate to good yields (47-87%). Another general application of trifluoroacetaldehyde is the synthesis of chiral α-substituted trifluoroethylamino compounds. In this synthesis, trifluoroacetaldehyde was first converted into the chiral trifluoromethyl tert-butyl sulfinimine, which was subjected to 1,2-nucleophilic addition reactions across its C{double bond, long}N double bond. The addition of phenyllithium afforded α-(phenyl)trifluoroethylamino derivative in 83% yield and with 96% de. Allylation and Reformatsky reactions produced the corresponding α-substituted trifluoroethylamino derivatives in 82 and 58% yields and with 90 and 91% de, respectively.

Evidence for a hydrogen abstraction mechanism in P450-catalyzed N-dealkylations

The experimental evidence presented in this manuscript suggest against the widely accepted single electron/proton transfer mechanism for P450 catalyzed N-dealkylations and provides strong support for a hydrogen atom abstraction mechanism.