Carboxamides alkylation

Amides are named by replacing the -oic acid or -ic acid suffix of the parent carboxylic acids with the suffix -amide, or hy replacing the -carboxylic acid ending with -carboxamide. Alkyl groups on nitrogen atoms are named as substituents, and are prefaced by N-or N,N-, followed by the name(s) of the alkyl group(s). 

One-letter abbreviations, pE, 5-oxoproline -NHj, C-terminal carboxamide. Alkylated on S. 

Despite the fact that one of the first pteridine syntheses was based on an intramolecular Hofmann carboxamide degradation of pyrazine-2,3-dicarboxamide by action of potassium hypobromite and leads to lumazine (equation 104), (07CB4857), pyrazine derivatives in general have not often been used because of availability problems. The reaction of alkyl... 

The reaction of the enamines of cyclic ketones with alkyl isocyanates, acyl isocyanates, phenyl isothiocyanates, and acyl isothiocyanates has also been reported 112). The products are the corresponding carboxamides. The products from the isothiocyanates have been utilized as intermediates in the preparation of various heterocyclic compounds 113). 

Dewar and Turchi carried out similar rearrangements of secondary and tertiary alkyl and aryl oxazole-4-carboxamides (5a-e) to the corresponding secondary and tertiary 5-aminooxazoles (6a-e). For example, they realized yields > 90% when the amide nitrogen is part of a heterocyclic ring system. 

The A-substituted derivatives of 4-oxo-4//-pyrido[l,2-n]pyrimidine-3-carboxamides and -3-acetamides and l,6-dimethyl-4-oxo-1,6,7,8-tetrahy-dro-4//-pyrido[l,2-n]pyrimidine-3-carboxamide were prepared by treatment of the appropriate 3-carboxylic acids and acetic acid, first with an alkyl chloroformate in the presence ofNEt3 in CHCI3 below — 10°C, then with an amine (98ACH515). A-Phenethyl and A-[2-(3,4-dimethoxyphenyl)ethyl] derivatives of 6-methyl-6,7,8,9-tetrahydro-4//-pyrido[l, 2-n]pyrimidine-3-acetamide were obtained in the reaction of 6-methyl-6,7,8,9-tetrahydro-4//-pyrido[l,2-n]pyrimidine-3-acetic acid and phenethylamines in boiling xylene under a H2O separator. Hydrazides of 4-oxo-4//- and 4-oxo-6,7,8,9-tetrahydro-4//-pyrido[l, 2-n]pyrimidine-3-acetic acid were prepared from the appropriate ester with H2NNH2 H2O in EtOH. Heating 4-oxo-4//- and 6-methyl-4-oxo-6,7,8,9-tetrahydro-4//-pyrido[l, 2-n]pyrimidine-3-acetic hydrazides in EtOH in the presence of excess Raney Ni afforded fhe appropriafe 4-oxo-6,7,8,9-fefrahydro-4//-pyrido[l,2-n]pyrimidine-3-acefa-mide. In the case of the 4-oxo-4// derivative, in addition to N-N bond... 

The respective amide was prepared from 7-substituted 5-oxo-2,3-dihydro-5//-pyrido[l,2,3-de]-l,4-benzoxazine-6-carboxylic acids via acid chlorides with different benzylamines (00M1P3). 6-Carboxamides were N-benzylated, and a side-chain phenolic hydroxy group was O-alkylated. 7-Aryl-5-oxo-2,3-dihydro-5//-pyrido[l, 2,3-r/e]-1,4-benzoxazine-6-carboxylic acid was obtained from the ethyl ester by alkalic hydrolysis. 

A number of diarylmethyl alkylpiperazines, such as, for example lidoflazine, have found use as coronary vasodilators for the treatment of angina. The most recent of these interestingly incorporates a 2,6-dichloroaniline moiety reminiscent of antiarrhythmic agents. Treatment of the piperazine carboxamide 124 with acetone leads to formation of the nitrogen analogue of an acetal, the aminal 125. Alkylation of the remaining secondary nitrogen with chloroamide 126 leads to the intermediate 127. Exposure to aqueous acid leads to hydrolysis of the aminal function... 

Reaction of 1,3-dicarbonyl compounds with IVJV-dimethylformamide dimethyl acetal followed by malonamide in the presence of sodium hydride gives 5,6-disubstituted 1,2-dihydro-2-oxopyridine-3-carboxamides, whereas reaction of the intermediate enamines with cyanothioacetamide or cyanoacetamide in the presence of piperidine provides 2-thioxopyridine-3-carboxamides and 4,5-disubstituted l,2-dihydro-2-oxopyridine-3-carboxamides, respectively <95S923>. P-Enaminonitriles 14 react with p-ketoesters and alkyl malonates, in the presence of stoichiometric amounts of tin(IV) chloride, to afford 4-aminopyiidines 15 and 4-amino-2-pyridones 16 <95T(51)12277>. 

The C-6 carboxamide analogues of zanamivir, represented by the general structure 24, provided an avenue to introduce more hydrophobic side-chains onto the dihydropyran scaffold to interact with the hydrophobic regions of subsites S4 and S5 (reviewed in Islam and von Itzstein 2007). The most active tertiary amides (24 = alkyl) showed comparable inhibitory activity to their glycerol side-... 

Importantly, there was a general marked selectivity for inhibition of influenza A over influenza B viral sialidases in the carboxamide series (e.g. as seen with 27) (Smith et al. 1996, 1998), determined from crystallographic and molecular modelling studies (Smith et al. 1996 Taylor et al. 1998) to be due to the relative abilities of each of the sialidases to absorb the structural changes required to accommodate the hydrophobic alkyl chains in the glycerol side-chain binding pocket. In influenza... 

The course of the reaction of phosphinous amides with carboxylic acid chlorides is dependent on the characteristics of the iV-residue. Thus with N-aryl compounds this reaction gives chlorophosphanes and carboxamides. With AT-alkyl analogs the primary reaction products have not been identified but they hydrolyzed to carboxaldehydes [120]. 

Pharmacokinetic studies of Ai-pyridinyl-indole-3-(alkyl)carboxamides and derivatives 95... 

Secondary amines, such as pyrrolidine, must be alkylated with care too polar a solvent leads to participation of a second nearby polymer-bound alkylant in the formation of a quaternary ammonium salt, along with the desired immobilized trialkyl amine. The exception, as seen above, is diisopropylamine, which refuses to displace tosylate even in the refluxing pure amine, or in hot dimethyl-formamide or other polar solvent, while metal diisopropylamide is notorious as a powerful non-nucleophilic base. However, carboxamide is not difficult to form from (carboxymethyl)polystyrene, again using toluenesulfonyl chloride as condensing agent this can then be reduced to (diisopropyl-ethylaminoethyl)polystyrene, which is of interest as a polymer-bound non-nucleophilic base. ... 

Phenyl-l,2,5-thiadiazole-3-carboxamide can be converted to the methyl 4-phenyl-l,2,4-thiadiazole-3-carboxylate with BF3-OEt2 in MeOH at reflux <2001H(55)75>. Alkyl substituents bearing a-chlorines can be dehalogenated with Pd/C-H2 in EtOH <1998JME4378>, or with Raney-Ni and H2 at atmospheric pressure in EtOH <1995USP5418240>. 

Rhodium(n) carboxamidates are clearly superior to all other types of catalysts in effecting highly chemo-, regio-, diastereo-, and enantioselective intramolecular C-H activation reactions of carbenoids derived from diazoacetates. Specifically, Rh2(4Y-MPPIM)4 is the catalyst of choice for C-H activation reactions of simple primary and secondary alkyl diazoacetates. Likewise, Rh2(4Y-MACIM)4 thus far has been the most successful catalyst with tertiary alkyl diazoacetates, whereas for primary acceptor-substituted diazoacetates with a pendant olefin side chain, Rh2(4A-MEOX)4 has proved to be highly selective. 

---