694495-47-1

Usage

InChI:InChI=1/C22H22F3N.ClH/c1-16(20-13-5-10-18-9-2-3-12-21(18)20)26-14-6-8-17-7-4-11-19(15-17)22(23,24)25;/h2-5,7,9-13,15-16,26H,6,8,14H2,1H3;1H/t16-;/m0./s1

Upstream product

• 145485-43-4 4-(3-(trifluoromethyl)phenyl)butanoic acid 
• 566938-58-7 1-(3-iodopropyl)-3-(trifluoromethyl)benzene 
• 10420-89-0 (S)-1-(1-Naphthyl)ethylamine 
• 1423-26-3 (meta-(trifluoromethyl)phenyl)boronic acid 
• 78573-45-2 3-[3-(trifluoromethyl)phenyl]propan-1-ol 
• 3886-70-2 (R)-1-(1-Naphthyl)ethylamine 
• 82258-76-2 1-(3-chloropropyl)-3-(trifluoromethyl)benzene 
• 871543-59-8 3-(3-(trifluoromethyl)phenyl)acrylaldehyde 
• 1207533-91-2 (R)-α-methyl-N-[3-[3-(trifluoromethyl)phenyl]propyl-2-ene]-1-naphthalenemethaneamine hydrochloride 
• 1073144-62-3 (1R)-1-(naphthalen-1-yl)ethanamine (R)-mandelate 
• 21172-43-0 methylsulfonyl-3-(3-trifluoromethylphenyl)propyl ester 
• 1245374-92-8 cinacalcet base 
• 401-78-5 3-bromo-1-trifluoromethylbenzene 
• 585-50-2 3-(3-trifluoromethylphenyl)propanoic acid 

Relevant academic research and scientific papers

BF3·Et2O as a metal-free catalyst for direct reductive amination of aldehydes with amines using formic acid as a reductant

A versatile metal- and base-free direct reductive amination of aldehydes with amines using formic acid as a reductant under the catalysis of inexpensive BF3·Et2O has been developed. A wide range of primary and secondary amines and diversely substituted aldehydes are compatible with this transformation, allowing facile access to various secondary and tertiary amines in high yields with wide functional group tolerance. Moreover, the method is convenient for the late-stage functionalization of bioactive compounds and preparation of commercialized drug molecules and biologically relevant N-heterocycles. The procedure has the advantages of simple operation and workup and easy scale-up, and does not require dry conditions, an inert atmosphere or a water scavenger. Mechanistic studies reveal the involvement of imine activation by BF3and hydride transfer from formic acid.

Enantioconvergent Cu-Catalyzed Radical C-N Coupling of Racemic Secondary Alkyl Halides to Access α-Chiral Primary Amines

α-Chiral alkyl primary amines are virtually universal synthetic precursors for all other α-chiral N-containing compounds ubiquitous in biological, pharmaceutical, and material sciences. The enantioselective amination of common alkyl halides with ammonia is appealing for potential rapid access to α-chiral primary amines, but has hitherto remained rare due to the multifaceted difficulties in using ammonia and the underdeveloped C(sp3)-N coupling. Here we demonstrate sulfoximines as excellent ammonia surrogates for enantioconvergent radical C-N coupling with diverse racemic secondary alkyl halides (>60 examples) by copper catalysis under mild thermal conditions. The reaction efficiently provides highly enantioenrichedN-alkyl sulfoximines (up to 99% yield and >99% ee) featuring secondary benzyl, propargyl, α-carbonyl alkyl, and α-cyano alkyl stereocenters. In addition, we have converted the masked α-chiral primary amines thus obtained to various synthetic building blocks, ligands, and drugs possessing α-chiral N-functionalities, such as carbamate, carboxylamide, secondary and tertiary amine, and oxazoline, with commonly seen α-substitution patterns. These results shine light on the potential of enantioconvergent radical cross-coupling as a general chiral carbon-heteroatom formation strategy.

Preparation method of cinacalcet hydrochloride

The invention discloses a method for preparing cinacalcet hydrochloride. The method comprises the following steps: performing condensation reaction on m-trifluoromethyl benzaldehyde serving as a starting raw material and acetaldehyde to prepare m-trifluoromethyl cinnamyl aldehyde, directly obtaining an oxalate intermediate from the m-trifluoromethyl cinnamyl aldehyde and R-1-(1-naphthyl) ethyl amine by a one-pot method to avoid impurity increase caused by separation of an unstable intermediate namely imine, desalting oxalate, carrying out Pd/C catalytic hydrogenation to obtain cinacalcet, and carrying out a reaction on cinacalcet and hydrochloric acid to finally obtain cinacalcet hydrochloride. The synthesis method disclosed by the invention is green, environment-friendly, economical and practical, simple to operate and more beneficial to industrial production.

Synthesis of Enantioenriched Amines by Iron-Catalysed Amination of Alcohols Employing at Least One Achiral Substrate

The synthesis of a broad range of enantioenriched amines by the direct Fe-catalysed coupling of amines with alcohols through the borrowing hydrogen strategy, while at least one of these substrates is achiral is reported. When starting from α-chiral amines and achiral alcohols, a wide range of enantioenriched amine products, including N-heterocyclic moieties can be obtained with complete retention of stereochemistry and the power of this method is demonstrated in the one-step synthesis of known pharmaceuticals from commercially available, simple enantiopure primary amines and achiral alcohols. It was also found that the use of β-branched enantioenriched primary alcohols and achiral amines as reaction partners leads to a partial loss of stereochemical integrity in the final product, however, a systematic optimization enabled partial retention of enantiopurity and possible parameters effecting for racemization were identified. (Figure presented.).

Two-Step Protocol for Iodotrimethylsilane-Mediated Deoxy-Functionalization of Alcohols

We have developed a two-step protocol for iodotrimethylsilane-mediated deoxy-functionalization of primary and secondary alcohols to afford products containing a C?N, C?S, or C?O bond. In the first step the alcohol undergoes iodination with iodotrimethylsilane, and in the second, the iodine atom is replaced by a N, S, or O nucleophile. Compared with traditional Mitsunobu reaction, non-acidic pre-nucleophiles can be used, and the reaction proceeds with retention of configuration. This operationally simple, highly efficient protocol can be used for some natural products and small-molecule drugs containing hydroxy-group.

Bisulfite Addition Compounds as Substrates for Reductive Aminations in Water

Highly valued products resulting from reductive aminations utilizing shelf-stable bisulfite addition compounds of aldehydes can be made under aqueous micellar catalysis conditions. Readily available α-picolineborane serves as the stoichiometric hydride source. Recycling of the aqueous reaction medium is easily accomplished, and several applications to targets in the pharmaceutical industry are documented.

Chemoselective Reductive Aminations in Aqueous Nanoreactors Using Parts per Million Level Pd/C Catalysis

Condensation in recyclable water between aldehydes or ketones and amines occurs smoothly within the hydrophobic cores of nanomicelles, resulting in imine formation that is subject to subsequent reduction leading, overall, to reductive amination. This micellar technology enables the synthesis of several types of pharmaceuticals, a new procedure that relies on only 2000 ppm (0.20 mol %) palladium from commercially available Pd/C. A broad range of substrates can be used under mild conditions, leading to high chemical yields of the desired secondary and tertiary amines.

Asymmetric reduction method of nitrogen-phosphonyl protected imine

The invention discloses an asymmetric reduction method of nitrogen phosphonyl protective imine. The nitrogen phosphonyl protective imine is reduced into chiral amine in a hydrogen atmosphere under theaction of a metal catalyst and alkali, and the metal catalyst is prepared from a metal iridium complex and a nitrogen-phosphorus chiral ligand. The method provided by the invention has the characteristics of high enantioselectivity, high yield and high conversion number (TON). The method can be used for synthesizing various substituted chiral amines, can be used as an important intermediate for preparing various medicines, and has important significance for industrial production of medicines.

Addition of Highly Polarized Organometallic Compounds to N-tert-Butanesulfinyl Imines in Deep Eutectic Solvents under Air: Preparation of Chiral Amines of Pharmaceutical Interest

Highly polarized organometallic compounds of s-block elements are added smoothly to chiral N-tert-butanesulfinyl imines in the biodegradable d-sorbitol/choline chloride eutectic mixture, thereby granting access to enantioenriched primary amines after quantitatively removing the sulfinyl group. The practicality of the method is further highlighted by proceeding at ambient temperature and under air, with very short reaction times (2 min), enabling the preparation of diastereoisomeric sulfinamides in very good yields (74–98 %) and with a broad substrate scope, and the possibility of scaling up the process. The method is demonstrated in the asymmetric syntheses of both the chiral amine side-chain of (R,R)-Formoterol (96 % ee) and the pharmaceutically relevant (R)-Cinacalcet (98 % ee).

Direct N-Alkylation/Fluoroalkylation of Amines Using Carboxylic Acids via Transition-Metal-Free Catalysis

A scalable protocol of direct N-mono/di-alkyl/fluoroalkylation of primary/secondary amines has been constructed with various carboxylic acids as coupling agents under the catalysis of a simple air-tolerant inorganic salt, K3PO4. Advantageous features include 100 examples, 10 drugs and drug-like amines, fluorinated complex tertiary amines, gram-scale synthesis and isotope-labelling amine, thus demonstrating the potential applicability in industry of this methodology. The involvement of relatively less reactive silicon-hydride compared with the traditional reactive metal-hydride or boron-hydride species required to reduce the amide intermediates presumably contributes to the remarkable functional group compatibility. (Figure presented.).