149098-91-9

Upstream product

• 140-10-3 (E)-3-phenylacrylic acid 
• 17105-71-4 N-methyl-N-benzylformamide 
• 103-67-3 benzyl-methyl-amine 
• 23776-87-6 2,5‐dioxopyrrolidin‐1‐yl cinnamate 
• 621-82-9 Cinnamic acid 
• 102-92-1 cinnamoyl chloride 
• 102-92-1 Cinnamoyl chloride 
• 122101-03-5 N-(o-bromobenzyl)-N-methyl-amide 
• 14371-10-9 (E)-3-phenylpropenal 

Downstream Products

• 66192-41-4 N-methyl-5-phenyl-1,2,4,5-tetrahydro-benzo[c]azepin-3-one 

Relevant academic research and scientific papers

A versatile biosynthetic approach to amide bond formation

The development of versatile and sustainable catalytic strategies for amide bond formation is a major objective for the pharmaceutical sector and the wider chemical industry. Herein, we report a biocatalytic approach to amide synthesis which exploits the diversity of Nature's amide bond forming enzymes, N-acyltransferases (NATs) and CoA ligases (CLs). By selecting combinations of NATs and CLs with desired substrate profiles, non-natural biocatalytic pathways can be built in a predictable fashion to allow access to structurally diverse secondary and tertiary amides in high yield using stoichiometric ratios of carboxylic acid and amine coupling partners. Transformations can be performed in vitro using isolated enzymes, or in vivo where reactions rely solely on cofactors generated by the cell. The utility of these whole cell systems is showcased through the preparative scale synthesis of a key intermediate of Losmapimod (GW856553X), a selective p38-mitogen activated protein kinase inhibitor.

METHOD FOR SYNTHESISING AMIDES

The present invention relates to a method for synthesising amides that is of general applicability. The method may be performed in vitro or in vivo. Cell lines for use in the in vivo methods also form aspects of the invention. The method for synthesising a non-natural amide comprises: a. reaction of a carboxylic acid with a naturally occurring CoA ligase or a variant thereof; and b. reaction of the product of step a with an amine in the presence of a naturally occurring acyltransferase or a variant thereof; with the proviso that where the CoA ligase and acyltransferase are both naturally occurring, they are not derived from the same source species and do not act sequentially in a metabolic pathway; and with the proviso that the non-natural product is not N-(E)-p-coumaroyl-3-hydroxyanthranilic acid or N-(E)-p-caffeoyl-3-hydroxyanthranilic acid. Further, a method for producing an active pharmaceutical ingredient by the aforementioned method and host cells for carrying out said methods are envisaged.

A copper-catalysed amidation of aldehydes via N-hydroxysuccinimide ester formation

A copper-catalysed oxidative amidation of aldehydes via N-hydroxysuccinimide ester formation is reported. The methodology employed to prepare amides directly from aldehydes has a very wide scope, is high yielding, and does not need dry conditions. This cross-coupling reaction appears to be simple and makes use of cheap, abundant and easily available reagents.

Copper-catalyzed oxidative coupling of carboxylic acids with formamides for the synthesis of α,β-unsaturated amides

A novel and efficient protocol for the synthesis of α,β- unsaturated amides has been developed using catalytic amount of Cu(OAc) 2 and TBHP as an available oxidant. Oxidative coupling of various unsaturated carboxylic acids with N,N-disubstituted formamides was examined to furnish the desired products in good yields.

The triflic acid-mediated cyclisation of N-benzylcinnamanilides

N-Benzylcinnamanilides cyclise with triflic acid to form 1-benzyl-4-aryl-2,4-dihydro-1H-quinolin-2-ones and 2,5-diaryl-benzazepin-3-ones. The product ratio is determined by the preferred orientation of the amide and by the electronics of the substituents. With ortho-substituted anilides, N-debenzylation also occurs to give 4-aryl-2,4-dihydro-1H-quinoline-2-ones.

The triflic acid-mediated cyclisation of N-benzyl-cinnamamides

N-Benzyl-cinnamamides cyclise with triflic acid to form 5-aryl-benzazepinones and/or cinnamamides.

SYNTHESIS OF OXINDOLES BY RADICAL CYCLISATION

Oxindoles are readily synthesised by intramolecular addition of aryl radicals to the α-position of α,β-unsaturated N-alkylamides.