61502-90-7

Usage

Uses

Used in Pharmaceutical Research and Development:
(9H-Fluoren-9-yl)methyl (pyrrolidin-2-ylmethyl)carbamate hydrochloride is used as a compound in pharmaceutical research and development for its potential role in drug design and discovery. Its unique structure and properties are being studied for possible applications in creating new medications.
Used in Drug Design and Discovery:
In the field of drug design and discovery, (9H-Fluoren-9-yl)methyl (pyrrolidin-2-ylmethyl)carbamate hydrochloride is used as a structural component for the development of novel therapeutic agents. Ongoing research is focused on understanding its biological activities and potential therapeutic uses, which may lead to the creation of new medications in the future.

Upstream product

• 39889-69-5 biphenyl-4-yl-acetyl chloride 
• 2350-89-2 p-vinylbiphenyl 
• 59793-29-2 methyl 2-(1,1'-biphenyl-4-yl)acetate 
• 5728-52-9 (4-biphenylyl)acetic acid 
• 1591-31-7 4-iodo-biphenyl 
• 92-52-4 biphenyl 
• 25789-56-4 ethyl 2-([1,1'-biphenyl]-4-yl)-2-hydroxyacetate 
• 14062-23-8 4-biphenylylacetic acid ethyl ester 
• 3218-36-8 4-Phenylbenzaldehyde 
• 1129550-73-7 C₁₅H₁₄O 
• 36099-26-0 2-([1,1′-biphenyl]-4-yl)oxirane 
• 31603-77-7 4-biphenylacetonitrile 
• 37729-18-3 2-(biphenyl-4-yl)ethanol 
• 264915-98-2 2-([1,1'-biphenyl]-4-yl)-N-methoxy-N-methylacetamide 

Downstream Products

• 1072896-68-4 p-methoxyphenyl (9-2-(4-biphenyl)ethylamino-3,5,9-trideoxy-5-glycolamido-D-glycero-α-D-galacto-2-nonulopyranosylonic acid)-(2->6)-β-D-galactopyranoside 
• 1147752-20-2 8-[[1-([1,1'-biphenyl]-4-ylmethyl)-2-oxo-2-[(2-phenylethyl)amino]ethyl](phenylmethyl)amino]-8-oxo-octanoic acid ethyl ester 
• 1431696-10-4 (E)-4-(3-(phenylsulfonyl)allyl)-1,1'-biphenyl 
• 1431696-16-0 (E)-4-(3-(phenylsulfonyl)prop-1-en-1-yl)-1,1'-biphenyl 
• 220211-94-9 5-phenyl-1H-inden-2(3H)-one 
• 70090-71-0 4-(prop-2-yn-1-yl)-1,1'-biphenyl 
• 349407-14-3 N-methyl-N-phenyl-[1,1'-biphenyl]-4-carboxamide 
• 149690-12-0 (2R,4S)-5-([1,1'-biphenyl]-4-yl)-4-amino-2-methylpentanoic acid ethyl ester hydrochloride 
• 31603-77-7 4-biphenylacetonitrile 

Relevant academic research and scientific papers

Synthetic Access to gem-Difluoropropargyl Vinyl Ethers and Their Application to Propargyl Claisen Rearrangement

With the increasing importance of fluorine to medicinal chemistry and other areas, methods to access various fluorinated compounds are needed. Herein, we report the synthesis of difluoropropargyl vinyl ethers from ketones and aldehydes using difluoropropargyl bromide dicobalt complexes. We applied difluoropropargyl vinyl ethers to the synthesis of difluorodienone or difluoroallene under thermal conditions and trifluoro-pyran under acid-catalyzed conditions.

Trifluoromethanesulfonyl azide as a bifunctional reagent for metal-free azidotrifluoromethylation of unactivated alkenes

Vicinal trifluoromethyl azides have widespread applications in organic synthesis and drug development. However, their preparation is generally limited to transition-metal-catalyzed three-component reactions. We report here a simple and metal-free method that rapidly provides these building blocks from abundant alkenes and trifluoromethanesulfonyl azide (N3SO2CF3). This unprecedented two-component reaction employs readily available N3SO2CF3as a bifunctional reagent to concurrently incorporate both CF3and N3groups, which avoids the use of their expensive and low atom economic precursors. A wide range of functional groups, including bio-relevant heterocycles and amino acids, were tolerated. Application of this method was further demonstrated by scale-up synthesis (5 mmol), product derivatization to CF3-containing medicinal chemistry motifs, as well as late-stage modification of natural product and drug derivatives.

1-(1-Arylethylpiperidin-4-yl)thymine analogs as antimycobacterial TMPK inhibitors

A series of Mycobacterium tuberculosis TMPK (MtbTMPK) inhibitors based on a reported compound 3 were synthesized and evaluated for their capacity to inhibit MtbTMPK catalytic activity and the growth of a virulent M. tuberculosis strain (H37Rv). Modifications of the scaffold of 3 failed to afford substantial improvements in MtbTMPK inhibitory activity and antimycobacterial activity. Optimization of the substitution pattern of the D ring of 3 resulted in compound 21j with improved MtbTMPK inhibitory potency (three-fold) and H37Rv growth inhibitory activity (two-fold). Moving the 3-chloro substituent of 21j to the para-position afforded isomer 21h, which, despite a 10-fold increase in IC50-value, displayed promising whole cell activity (minimum inhibitory concentration (MIC) = 12.5 μM).

Selective N1/N4 1,4-Cycloaddition of 1,2,4,5-Tetrazines Enabled by Solvent Hydrogen Bonding

An unprecedented 1,4-cycloaddition (vs 3,6-cycloaddition) of 1,2,4,5-tetrazines is described with preformed or in situ generated aryl-conjugated enamines promoted by the solvent hydrogen bonding of hexafluoroisopropanol (HFIP) that is conducted under mild reaction conditions (0.1 M HFIP, 25 °C, 12 h). The reaction constitutes a formal [4 + 2] cycloaddition across the two nitrogen atoms (N1/N4) of the 1,2,4,5-tetrazine followed by a formal retro [4 + 2] cycloaddition loss of a nitrile and aromatization to generate a 1,2,4-triazine derivative. The factors that impact the remarkable change in the reaction mode, optimization of reaction parameters, the scope and simplification of its implementation through in situ enamine generation from aldehydes and ketones, the reaction scope for 3,6-bis(thiomethyl)-1,2,4,5-tetrazine, a survey of participating 1,2,4,5-tetrazines, and key mechanistic insights into this reaction are detailed. Given its simplicity and breath, the study establishes a novel method for the simple and efficient one-step synthesis of 1,2,4-triazines under mild conditions from readily accessible starting materials. Whereas alternative protic solvents (e.g., MeOH vs HFIP) provide products of the conventional 3,6-cycoladdition, the enhanced hydrogen bonding capability of HFIP uniquely results in promotion of the unprecedented formal 1,4-cycloaddition. As such, the studies represent an example of not just an enhancement in the rate or efficiency of a heterocyclic azadiene cycloaddition by hydrogen bonding catalysis but also the first to alter the mode (N1/N4 vs C3/C6) of cycloaddition.

Stereoselective Synthesis of Vinylboronates by Rh-Catalyzed Borylation of Stereoisomeric Mixtures

The stereoselective preparation of vinylboronates via rhodium-catalyzed borylation of E/Z mixtures of vinyl actetates is described, and this method was also extended to synthesis of vinyldiboronates. These transformations feature high functional group compatibility and mild reaction conditions. Control experiments support a mechanism that involved a Rh-catalyzed borylation-isomerization sequence. The isomerization of (Z)-vinylboronates to (E)-isomers was also demonstrated.

Preparation method of sacubitril

The invention discloses a preparation method of sacubitril. The method comprises the following steps a-e of the synthesis route, the formula is shown in the description, wherein R is hydroxyl protecting group. According to the method, the easily-obtained compound as shown in formula 1 and the easily-obtained compound as shown in formula 2 are used as the primary raw materials; the five steps are carried out to obtain the sacubitril by reaction; the whole route is simple in operation, safe, free from pollution, free from special requirements for equipment, low in production cost, high in yield,and suitable for industrial production.

Manganese-Catalyzed Dual-Deoxygenative Coupling of Primary Alcohols with 2-Arylethanols

Reported herein is a general and efficient dual-deoxygenative coupling of primary alcohols with 2-arylethanols catalyzed by a well-defined Mn/PNP pincer complex. This reaction is the first example of the catalytic dual-deoxygenation of alcohols using a non-noble-metal catalyst. Both deoxygenative homocoupling of 2-arylethanols (17 examples) and their deoxygenative cross-coupling with other primary alcohols (20 examples) proceeded smoothly to form the corresponding alkenes by a dehydrogenation and deformylation reaction sequence.

One-Pot Preparation of C1-Homologated Aliphatic Nitriles from Aldehydes through a Wittig Reaction under Metal-Cyanide-Free Conditions

A one-pot protocol to obtain C1-homologated aliphatic nitriles was achieved by treating aromatic and aliphatic aldehydes with the (methoxymethyl)triphenylphosphonium ylide followed by hydrolysis of the resulting methyl vinyl ethers with pTsOH (Ts = para-toluenesulfonyl) and treatment with molecular iodine and aqueous ammonia under metal cyanide free conditions. Neopentyl-type nitriles, which could not be obtained by conventional methods that involved conversion of the neopentyl alcohol into a tosylate and treatment with metal cyanide, were successfully obtained by using the present method.

NEW PROCESSES AND INTERMEDIATES USEFUL IN SYNTHESIS OF NEP INHIBITORS

The invention relates to a novel process, novel process steps and novel intermediates useful in the synthesis of pharmaceutically active compounds, in particular neutral endopeptidase (NEP) inhibitors such as sacubitril, and prodrugs thereof.

Synthesis of a Precursor to Sacubitril Using Enabling Technologies

An efficient preparation of a precursor to the neprilysin inhibitor sacubitril is described. The convergent synthesis features a diastereoselective Reformatsky-type carbethoxyallylation and a rhodium-catalyzed stereoselective hydrogenation for installation of the two key stereocenters. Moreover, by integrating machine-assisted methods with batch processes, this procedure allows a safe and rapid production of the key intermediates which are promptly transformed to the target molecule (3·HCl) over 7 steps in 54% overall yield.