146492-49-1

Upstream product

• 2627-86-3 (S)-1-phenyl-ethylamine 
• 13734-34-4 N-tert-butoxycarbonyl-L-phenylalanine 
• 7535-56-0 N-t-butoxycarbonyl-L-phenylalanine 4-nitrophenyl ester 
• 914955-62-7 [1-(4-methylbenzenesulfonyl)-2-phenylethyl]carbamic acid tert-butyl ester 
• 17279-30-0 (S)-(-)-α-methylbenzylamine hydrochloride 

Downstream Products

• 174007-71-7 (S)-2-Amino-3-phenyl-N-((S)-1-phenyl-ethyl)-propionamide 
• 174174-68-6 {(R)-2-(1-Formyl-1H-indol-3-yl)-1-[(S)-2-phenyl-1-((S)-1-phenyl-ethylcarbamoyl)-ethylcarbamoyl]-ethyl}-carbamic acid tert-butyl ester 
• 174174-72-2 ((1S,2R)-1-{(R)-2-(1-Formyl-1H-indol-3-yl)-1-[(S)-2-phenyl-1-((S)-1-phenyl-ethylcarbamoyl)-ethylcarbamoyl]-ethylcarbamoyl}-2-hydroxy-propyl)-carbamic acid tert-butyl ester 

Relevant academic research and scientific papers

Comprehensive Study of the Organic-Solvent-Free CDI-Mediated Acylation of Various Nucleophiles by Mechanochemistry

Acylation reactions are ubiquitous in the synthesis of natural products and biologically active compounds. Unfortunately, these reactions often require the use of large quantities of volatile and/or toxic solvents, either for the reaction, purification or isolation of the products. Herein we describe and discuss the possibility of completely eliminating the use of organic solvents for the synthesis, purification and isolation of products resulting from the acylation of amines and other nucleophiles. Thus, utilisation of N,N′-carbonyldiimidazole (CDI) allows efficient coupling between carboxylic acids and various nucleophiles under solvent-free mechanical agitation, and water-assisted grinding enables both the purification and isolation of pure products. Critical parameters such as the physical state and water solubility of the products, milling material, type of agitation (vibratory or planetary) as well as contamination from wear are analysed and discussed. In addition, original organic-solvent-free conditions are proposed to overcome the limitations of this approach. The calculations of various green metrics are included, highlighting the particularly low environmental impact of this strategy.

Highly modular dipeptide-like organocatalysts for direct asymmetric aldol reactions in brine

A novel series of dipeptide-like organocatalysts derived from proline, amino acids and primary amines have been prepared for direct asymmetric aldol reactions between various aromatic aldehydes and acetone to afford aldol products in good yields (up to 82%) and moderate enantioselectivities (up to 67% ee) with only 1 mol% of catalyst-loading in brine. Under the same conditions, the direct asymmetric aldol reactions of aromatic aldehydes and cyclohexanone give aldol products with high yields (up to 91%) and moderate to good enantioselectivities (up to 88% ee) and excellent diastereoselectivities (up to 99% dr). These organocatalysts are easily synthesized from commercially available materials in multi-gram scale with high modularity in their structural and stereogenic properties.

Identification and SAR of Glycine Benzamides as Potent Agonists for the GPR139 Receptor

A focused high throughput screening for GPR139 was completed for a select 100K compounds, and new agonist leads were identified. Subsequent analysis and structure-activity relationship studies identified (S)-3-chloro-N-(2-oxo-2-((1-phenylethyl)amino)ethyl

Thioesterifications Free of Activating Agent and Thiol: A Three-Component Reaction of Carboxylic Acids, Thioureas, and Michael Acceptors

An amine-catalyzed, one-pot synthesis of thioesters directly from carboxylic acids, thioureas, and Michael acceptors is described. This process was further improved by use of 1-[2-(methylamino)ethyl]-3-phenylthiourea (4) as the catalyst. Aromatic and aliphatic carboxylic acids with functional groups are compatible with this process, and both α,β-unsaturated esters and ketones can be the Michael acceptors for this reaction. The progress of this reaction was monitored by 1H NMR, and a reaction mechanism is proposed.

Enantioselective synthesis of d-α-amino amides from aliphatic aldehydes

Peptides consisting of d-amino amides are highly represented among both biologically active natural products and non-natural small molecules used in therapeutic development. Chemical synthesis of d-amino amides most often involves approaches based on enzy

Synthesis of highly substituted imidazolidine-2,4-dione (Hydantoin) through Tf2O-mediated dual activation of Boc-protected dipeptidyl compounds

Highly substituted chiral hydantoins were readily synthesized from simple dipeptides in a single step under mild conditions. This reaction proceeded through the dual activation of an amide and a tert-butyloxycarbonyl (Boc) protecting group by Tf2O-pyridine. This method was successfully applied in the preparation of a variety of biologically active compounds, including drug analogs and natural products.

Mechanosynthesis of amides in the total absence of organic solvent from reaction to product recovery

The synthesis of various amides has been realised avoiding the use of any organic solvent from activation of carboxylic acids with CDI to isolation of the amides. Mechanochemistry was the key point of the process allowing rapid formation of the amide bond and efficient water-based purification of the final products.

Automated synthesis and purification of amides: Exploitation of automated solid phase extraction in organic synthesis

Automated parallel synthesis of small organic molecules, either as single entities or as mixtures, offers the potential for the rapid optimization of physical and biological properties of a molecule Currently, emphasis has been placed on solid phase synthesis technology to accomplish the rapid preparation of large numbers of molecules. Automated solution phase synthesis is an alternative approach which has the advantages of having shorter development times and being more amenable to scaleup. Utilizing commercially available liquid handlers for reaction setup and exploiting automated solid phase extraction for product purification, a procedure has been developed to prepare and purify up to 100 amide analogs, simultaneously. Both carbodiimide mediated couplings and p-nitro-phenyl ester displacements have been carried out using this procedure. Product amides having overall neutral or basic character have been prepared in good yield and with good to excellent purities.

Synthesis and in vitro activities of highly potent and selective tripeptide antagonists of the neurokinin NK-1 receptor

We report on the synthesis and the pharmacological properties of a new series of tachykinin antagonists based on the tripeptide Ac-Thr-D-Trp(CHO)-Phe-N(Me)-Bzl (1, FR113680) partly modified on the C-terminal amide part. Stereochemistry around the benzilic