Carbonyl carboxamide

C-H-Oleflnation. Pd(II)-mediated aromatic C(sp2)-H olefi-nation occurs via a tandem reaction with tosylamide as directing group and bond formation partner (eq 12). The reaction tolerates different substituents at the phenyl ring such as methyl, methoxy, bromine, fluorine, trifluoromethyl and biphenyl with yields from 64% to 87%. Further, instead of CO Bu aliphatic esters as well as carbonyl, carboxamide, halogens, and aryl substitutents are suitable substrates. ... 

The thiation procedure described here is an example of a general synthetic method for the conversion of carbonyl to thiocarbonyl groups. Similar transformations have been carried out with ketones, carboxamides,esters,thioesters, 1 actones, " thiol actones, - imides, enaminones, and protected peptides. ... 

Et2NH (25 mL. large excess) was cautiously added to a cooled stirred suspension of crude 5-oxo-4-phenyl-4,5-dihydro-l//-l,2,4-benzotriazcpine-3-carbonyl chloride (10, R1 = Ph, R2 = H 5.0 g, 17 mmol) in benzene (100 mL) below 25 C and stirring was continued for 2h. H20 was added to dissolve the F,t2NH HOI formed and the insoluble yellow residue, A%V-diethyl-5-oxo-4-phenyl-4,5-dihydro-l//-l,2,4-benzodiazepine-3-carboxamide (llg) was collected, washed with H20 and recrystallizcd (95% EtOH) yield 4.0 g (70%) mp 202-204 C. 

Inhibitors for proteases plasmepsin I and II of the malaria parasite Plasmodium falciparum, with a good plasmepsin/human protease cathepsin D selectivity, have been identified via library construction involving rapid microwave-accelerated Suzuki reactions [57]. The phenyl ring of the biphenyl unit in the lead compound M-((lS)-l- [((lS,2S)-3- [(lS)-2-amino-l-(4-phenyl-benzyl)-2-oxoethyl]amino -2-hydroxy-l-phenoxypropyl)amino]carbonyl -2-methylpropyl)pyridine-2-carboxamide has been altered by performing Suzuki reactions on N-((lS)-l- [((lS,2S)-3- [(lS)-2-amino-l-(4-bromobenzyl)-2-oxoethyl]amino -2-hydroxy-l-phenoxypropyl)amino]carbonyl -2-methyl-propyl)pyridine-2-carboxamide (Scheme 37). In particular, a 2-benzofuryl moiety proved to be interesting since a Ki value of 13 nM for plasmepsin I and... 

CN A-[5-[[(3-amino-3-iminopropyl)amino]carbonyl]-l-methyl-l//-pyrrol-3-yl]-4-[[[4-(rormylamino)-methyl-l//-pyrrol-2-yl]carbonyl]amino]-l-methyl-lf/-pyrrole-2-carboxamide... 

Patent applications from Pfizer disclosed 1,5-diaryl-pyrazoles bearing bioisosteric replacements for the 3-carboxamide moiety. One application showed that the amide could be replaced by a-aminoketones as exemplified by compound (416) [284]. The corresponding alcohols and their ethers were also described, including compounds that allowed the amine substituent and ether to form a ring system, such as a morpholine unit. This application also allowed for the replacement of the 1,5-diaryl-pyrazole by a 1,2-diaryl-imidazole bearing a 3-carbonyl substituent, as exemplified by compound (417). A further patent application from Pfizer claims compounds in which imidazoles replace the 3-carboxamide moiety in the 1,5-diaryl-pyrazole... 

In the HMBC spectrum this NH proton exhibited 3/(CH) correlation to the C3" (5174.15) and 2/(CH) interaction to the C13 (5165.48) carbonyl, the latter in turn showing 2/(CH) interaction with H12(56.05). Thus it became clear that a carboxamide group linked the conjugated triene and the cyclopentenone unit. A 2/(CH) coupling of the triene terminus H7 to C4 (5jj/5c 5.86/71.20) established the point of attachment of the triene unit to C4. An observed NOE interaction between the H7 and H5 lent further support to this attachment and was suggestive of proximal orientation of the trans-A1 bond to the epoxy unit in the most preferred conformation. The absolute configuration at C4 was not established. 

CARBONYLATION REACTIONS LEADING TO ALIPHATIC CARBOXYLIC ACIDS, ESTERS, LACTONES AND CARBOXAMIDES... 

Fig. 6 Ellipsometric analysis of films containing various mixtures of amines and carboxylic acids 3-PAA/lN (ca. 55% -CO2H) 3-PAA/3N (ca. 17% -CO2H) and 3-PAA/6N (no - CO2H groups could be distinguished from carboxamide carbonyl peak in the FTIR-ERS spectrum). The IN, 3N and 6N refers to the number of times the amidation in Eq. 3 was repeated using NH2CH2CH2N(CH3) as the amidating reagent...

---