The Medicinal Chemist’s Toolbox: An Analysis of Reactions Used in the Pursuit of Drug Candidates

Roughley, Stephen D.; Jordan, Allan M.

doi:10.1021/jm200187y

Cited by 2,224 publications

(1,548 citation statements)

References 155 publications

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“…2 It has been estimated that 16% of all reactions involved in the synthesis of modern pharmaceuticals was the acylation of an amine, which makes it the most commonly performed reaction in this field. 3 Polymers 25 based on the amide linkage are of importance in a wide range of applications, from everyday materials such as nylons, to more advanced uses in drug delivery systems, adhesives and wound healing. 4 In addition, the amide bond is commonly found as a key structural element in agrochemicals and in products from the fine 30 chemicals industry.…”

Section: Introductionmentioning

confidence: 99%

“…15 Electron-poor aryl amines and secondary amines however, required longer reaction times (4-15h) in order to obtain useful yields. Other Lewis acidic metal salts such as SnCl 2 , LaCl 3 and La(OTf) 3 were equally efficient as catalysts for the synthesis of formanilide (>90% yield in all cases). In absence of a catalyst, the 20 reaction did not proceed.…”

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confidence: 98%

“…106 The metal catalysts could be reused up to 8 times by recycling of the ionic liquid after decantation and extraction of the amide products. In addition, Sb(OEt) 3 …”

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confidence: 99%

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Catalytic amide formation from non-activated carboxylic acids and amines

et al. 2014

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The amide functionality is found in a wide variety of biological and synthetic structures such as proteins, polymers, pesticides and pharmaceuticals. Due to the fact that synthetic amides are still mainly produced by the aid of coupling reagents with poor atom-economy, the direct catalytic formation of amides from carboxylic acids and amines has become a field of emerging importance. A general, efficient and selective catalytic method for this transformation would meet well with the increasing criterias for green 10 chemistry. This review covers catalytic and synthetically relevant methods for direct condensation of carboxylic acids and amines. A comprehensive overview of homogeneous and heterogeneous catalytic methods is presented, covering biocatalysis, Lewis acid catalysts based on boron and metals as well an assortment of other types of catalysts.

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Section: Introductionmentioning

confidence: 99%

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Catalytic amide formation from non-activated carboxylic acids and amines

et al. 2014

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“…2 The synthesis of sulfonamides is most commonly achieved by the reaction of a sulfonyl chloride (R 1 SO 2 Cl) with an amine (HNR 2 R 3 ) under basic conditions. 3 However, the application of substituted sulfonyl chlorides that incorporate polar groups, to offer additional specific binding interactions and to attenuate the overall lipophilicity of the drug candidate, can be hampered due to limited availability.…”

Section: Discussionmentioning

confidence: 99%

“…The white crystals are washed with two portions of cold water (50 mL) and dried under high vacuum for 12 h (<1 mmHg) to give O-(4-cyano-2-methoxyphenyl) dimethylcarbamothioate (1) as white crystals (28.2 g, 71%) (Notes 10, 11, and 12). (2). To a 250 mL single-necked round-bottomed flask fitted with a reflux condenser and a 25 x 15 mm oval-shaped Teflon-coated magnetic stir bar is added O-(4-cyano-2-methoxyphenyl) dimethylcarbamothioate (1) (28.0 g, 118 mmol, 1.0 equiv).…”

Section: Procedures (Note 1)mentioning

confidence: 99%

4‐Cyano‐2‐Methoxybenzenesulfonyl Chloride

Bayle

2018

Organic Syntheses

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Procedures yielding O ‐(4‐cyano‐2‐methoxyphenyl) dimethylcarbamothioate ( 1 ) as white crystals, S ‐(4‐cyano‐2‐methoxy‐phenyl)dimethylcarbamothioate ( 2 ) as a pure product, 4‐mercapto‐3‐methoxybenzonitrile ( 3 ) (14.4 g, 90%) as a slightly pungent white solid, and 4‐cyano‐2‐methoxybenzenesulfonyl chloride ( 4 ) as a yellow solid are presented. The chapter concludes with a discussion on sulfonamide functional group and related syntheses.

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Palladium‐Catalyzed Amination of Aryl Halides

et al. 2019

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Palladium‐catalyzed amination of aryl halides is widely used in the synthesis of N ‐aryl amine derivatives. N ‐Aryl amines have important applications as pharmaceuticals, agricultural chemicals, and electronic materials. This chapter provides a summary of the mechanism, the optimal choice of catalyst, and the scope of this important reaction. Application to the arylation of ammonia, amines, amide derivatives, hydrazines, NH imines, and azoles are discussed. The strengths and limitations of the palladium‐catalyzed methodology are compared to nickel‐ and copper‐catalyzed amine arylation methods. Examples of the use of palladium‐catalyzed amine arylation in the synthesis of pharmaceutical intermediates and natural products are highlighted.

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The Medicinal Chemist’s Toolbox: An Analysis of Reactions Used in the Pursuit of Drug Candidates

Cited by 2,224 publications

References 155 publications

Catalytic amide formation from non-activated carboxylic acids and amines

Catalytic amide formation from non-activated carboxylic acids and amines

4‐Cyano‐2‐Methoxybenzenesulfonyl Chloride

Palladium‐Catalyzed Amination of Aryl Halides

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