N-Acyl-3,3-difluoro-2-oxoindoles as versatile intermediates for the preparation of different 2,2-difluorophenylacetic derivatives

Abstract

Este trabalho descreve a versatilidade sintética dos derivados N-Acil-3,3-diflúor-2-oxoindóis, obtidos a partir da reação de N-acilisatinas com dietilaminotrifluoreto de enxofre (DAST) que, através da reação com diferentes nucleófilos, promovem a abertura do anel heterocíclico, levando à formação de vários produtos. A reação de N-Acil-3,3-diflúor-2-oxoindóis com água fornece os ácidos 2-(2-N-acilfenil)-2,2-difluoracéticos e com álcoóis fornece os ésteres correspondentes. Reações com aminas e glicina levam à formação das correspondentes amidas 2-(2-N-acilfenil)-2,2-difluoracetamidas. Na reação com tiossemicarbazidas os derivados difluortiossemicarbazidas são obtidos. Estes últimos sofrem uma ciclização catalisada por ácido para fornecerThis paper describes the versatility of N-Acyl-3,3-difluoro-2-oxoindoles, obtained from the the reaction of N-acylisatins with (diethylamino)sulphur trifluoride (DAST) which, on opening of the heterocyclic ring by reactions with nucleophiles, lead to the formation of a variety of products: reaction with water yields 2-(2-amidoacyl)-2,2-difluoroacetic acids, with alcohols yields alkyl 2-(2-amidoacyl)-2,2-difluoroacetates, with amines and glycine yields 2-(2-amidoacyl)-2,2-difluoroacetamides and with thiosemicarbazides yields difluorothiosemicarbazide derivatives. The latter undergo acid-catalysed cyclizations to yield N- (2-((5-aminoaryl-1,3,4-thiadiazol-2-yl) difluoromethyl)-4-(R)-phenyl)acetamide. The X-ray structure of N- (2-((5-amino-1,3,4-thiadiazol-2-yl)difluoromethyl)-4-methylphenyl)acetamide has been determined.

Synthesis of β‐Substituted Porphyrin Derivatives Containing Heterocyclic Moieties as Potential Photosensitizers Against Cutaneous Leishmaniasis

“…The required amino heterocycles 3a – d were prepared according to the methodology described in the literature 14–16…”

“…It was considered that such products could be obtained from imine precursors. This has been carried out by coupling β‐formylporphyrins 1 and 2 to amino heterocycles, such as the aminotriazole 3a ,14 isoniazid (pyridine‐4‐carbohydrazide, 3b )15 and the aminothiadiazoles 3c and 3d 16 (Figure 1), followed by imine reduction.…”

OxymaPure/DIC: An Efficient Reagent for the Synthesis of a Novel Series of 4-[2-(2-Acetylaminophenyl)-2-oxo-acetylamino] Benzoyl Amino Acid Ester Derivatives

“…Parallel with the application of the α-ketoamide moiety in medicinal chemistry, numerous synthetic methods have been described [7,8,9,10,11,12,13,14,15,16,17,18,19,20,21]. Several authors have demonstrated that the synthesis of the α-ketoamide fragment can be achieved by ring opening of N -acetylisatin ( 1 ) by the attack of an amine at C2-carbonyl group of N -acetylisatin (Scheme 1) [22,23,24,25,26,27]. Recently, Cheah et al [28,29] reported the reaction of N -acetylisatin with L-α-amino acid esters as a novel class of N -glyoxylamide peptide mimics.…”

An Efficient and Mild Method for the Synthesis and Hydrazinolysis of N‐Glyoxylamino Acid Esters

“…In parallel with the application of the glyoxylamide in medicinal chemistry, numerous synthetic methods have been described in the literature [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. Other authors have also reported that synthesis of the glyoxylamide fragment could be achieved by the ring opening of Nacetylisatin 1 by attacking an amine at C2-carbonyl group of N-acetylisatin (Scheme 1) [27][28][29][30][31][32][33][34][35].…”