129254-76-8

Usage

Uses

Used in Pharmaceutical Industry:
1-BroMo-3-[3-(trifluoroMethyl)phenyl]propane is used as a key intermediate in the synthesis of Cinacalcet Hydrochloride (C441800) for the treatment of secondary hyperparathyroidism. It plays a crucial role in the development of this medication, which helps regulate the levels of calcium and parathyroid hormone in patients with this condition.

Upstream product

• 401-78-5 3-bromo-1-trifluoromethylbenzene 
• 294856-02-3 methyl 3-(3-(trifluoromethyl)phenyl)propanoate 
• 585-50-2 3-(3-trifluoromethylphenyl)propanoic acid 
• 779-89-5 3-(trifluoromethyl)cinnamic acid 
• 454-89-7 3-Trifluoromethylbenzaldehyde 
• 78573-45-2 3-[3-(trifluoromethyl)phenyl]propan-1-ol 

Downstream Products

• 226256-56-0 cinacalcet 
• 364782-34-3 cinacalcet hydrochloride 
• 1217809-88-5 N-(1-(naphthalen-1-yl)ethyl)-3-(3-(trifluoromethyl)phenyl)propan-1-amine hydrochloride 
• 1271930-15-4 (R)-(1-naphthalen-1-ylethyl)-N,N-bis[3-(3-trifluoromethylphenyl)propyl]amine 
• 1245374-92-8 cinacalcet base 
• 1093172-43-0 [2,2-dimethyl-5-(2-{3-trifluoromethyl-4-[3-(3-trifluoromethylphenyl)propoxy]phenyl}ethyl)-1,3-dioxan-5-yl]carbamic acid t-butyl ester 
• 129255-25-0 1-(3-trifluoromethylphenyl)-4-(3-methyl-pyridin-4-yl)-pentane 
• 129255-24-9 1-(3-trifluoromethylphenyl)-4-(3-ethyl-pyridin-4-yl)-butane 

Relevant academic research and scientific papers

Boron tribromide as a reagent for anti-Markovnikov addition of HBr to cyclopropanes

Although radical formation from a trialkylborane is well documented, the analogous reaction mode is unknown for trihaloboranes. We have discovered the generation of bromine radicals from boron tribromide and simple proton sources, such as water ortert-butanol, under open-flask conditions. Cyclopropanes bearing a variety of substituents were hydro- and deuterio-brominated to furnish anti-Markovnikov products in a highly regioselective fashion. NMR mechanistic studies and DFT calculations point to a radical pathway instead of the conventional ionic mechanism expected for BBr3

Synthesis of α-Substituted Primary Benzylamines through Copper-Catalyzed Cross-Dehydrogenative Coupling

A copper-catalyzed route to α-substituted, primary benzylamines by C-H functionalization of alkylarenes is described. The method directly affords the amine hydrochloride salt. Catalyst loadings down to 0.1 mol % in combination with scalability, insensitivity to air and moisture, and no need for column chromatography makes the procedure highly practical. The facile synthesis of the racemate of a blockbuster drug highlights the relevance for the development of pharmaceuticals. Preliminary mechanistic data are also included.

Chemical modification-mediated optimisation of bronchodilatory activity of mepenzolate, a muscarinic receptor antagonist with anti-inflammatory activity

The treatment for patients with chronic obstructive pulmonary disease (COPD) usually involves a combination of anti-inflammatory and bronchodilatory drugs. We recently found that mepenzolate bromide (1) and its derivative, 3-(2-hydroxy-2, 2-diphenylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane bromide (5), have both anti-inflammatory and bronchodilatory activities. We chemically modified 5 with a view to obtain derivatives with both anti-inflammatory and longer-lasting bronchodilatory activities. Among the synthesized compounds, (R)-(–)-12 ((R)-3-(2-hydroxy-2,2-diphenylacetoxy)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octane bromide) showed the highest affinity in vitro for the human muscarinic M3 receptor (hM3R). Compared to 1 and 5, (R)-(–)-12 exhibited longer-lasting bronchodilatory activity and equivalent anti-inflammatory effect in mice. The long-term intratracheal administration of (R)-(–)-12 suppressed porcine pancreatic elastase-induced pulmonary emphysema in mice, whereas the same procedure with a long-acting muscarinic antagonist used clinically (tiotropium bromide) did not. These results suggest that (R)-(–)-12 might be therapeutically beneficial for use with COPD patients given the improved effects seen against both inflammatory pulmonary emphysema and airflow limitation in this animal model.

Remote migratory cross-electrophile coupling and olefin hydroarylation reactions enabled by in situ generation of nih

A highly efficient strategy for remote reductive cross-electrophile coupling has been developed through the ligand-controlled nickel migration/arylation. This general protocol allows the use of abundant and bench-stable alkyl bromides and aryl bromides for the synthesis of a wide range of structurally diverse 1, 1-diarylalkanes in excellent yields and high regioselectivities under mild conditions. We also demonstrated that alkyl bromide could be replaced by the proposed olefin intermediate while using n-propyl bromide/Mn0 as a potential hydride source.

Hydrochloric acid and intermediates [...] the synthetic method of the compound of

The invention provides a synthetic method of cinacalcet hydrochloride intermediate compound meta-trifluoro methyl phenylpropyl bromine and cinacalcet hydrochloride. According to the synthetic method, synthetic technology of intermediate compound meta-trifluoro methyl phenylpropyl bromine is optimized, so that yield and purity of meta-trifluoro methyl phenylpropyl bromine and cinacalcet hydrochloride are improved significantly, product quality is ensured, raw material utilization ratio is increased, and product cost is reduced effectively.

A novel asymmetric synthesis of cinacalcet hydrochloride

A novel route to asymmetric synthesis of cinacalcet hydrochloride by the application of (R)-tert-butanesulfinamide and regioselective N-alkylation of the naphthyl ethyl sulfinamide intermediate is described.

Industrial application of the forster reaction: Novel one-pot synthesis of cinacalcet hydrochloride, a calcimimetic agent

Described is a new, practical, and one-pot process, based on the Forster reaction, for the synthesis of cinacalcet hydrochloride (1), a calcimimetic agent and calcium-sensing receptor antagonist. The synthesis comprises the condensation of (1R)-(+)-1-naphthylethyl amine (2) with benzaldehyde (3) followed by reaction of obtained Schiff's base 4 with 1-(3-halopropyl)-3- (trifluoromethyl)benzene (5) to provide highly unstable iminium salt 6. Subsequent hydrolysis of 6 with water in the same pot yielded cinacalcet. The treatment of cinacalcet with hydrochloric acid during the workup process furnished 1 with an overall yield of around 60%. Our synthetic approach for 1, discussed in this report demonstrates industrial application of the century-old, unexplored name reaction, "Forster's Reaction" or Forster-Decker synthesis.

AMINE COMPOUND AND PHARMACEUTICAL USE THEREOF

Provided is a novel amine compound represented by the following formula (I) having a superior peripheral blood lymphocyte decreasing action and superior in the immunosuppressive action, rejection suppressive action and the like, which shows decreased side effects of, for example, bradycardia and the like, or a pharmaceutically acceptable acid addition salt thereof, or a hydrate thereof, or a solvate thereof. wherein each symbol is as defined in the specification.

PROCESSES FOR THE PREPARATION OF CINACALCET

There are described several processes for making a free base of cinacalcet. One of the described processes goes through an intermediate of the formula (II) where R1 and R2 are both hydrogen, or R1 and R2, together, form a double bond.