2-carbamoyl-4- imidazole

Bristol-Myers Squibb has recently disclosed two different series of carbamate-based FAAH inhibitors. The first of these is a series of 4,5-diaryl-imidazoles in which 30 compounds are specifically claimed, an example being compound (57). This compound is reported to have an IC50 value of < 10 nM. In addition, (57) was also active in vivo in rodent models of chemo-induced, thermal and neuropathic pain [72]. The second series of compounds is based on oxime carbamoyl FAAH inhibitors such as (58). Compound (58) is reported to have an IC50 value of < 10 nM and activity in rodent models of inflammatory pain, thermal pain and inflammatory oedema [73]. 

The concept of in situ liberation of carbon monoxide would be even more attractive if a metal-free material could serve as the carbon monoxide source. In the ideal carbonylation method, the organic solvent itself could be exploited for controlled generation of carbon monoxide. In 2002, Wan et al. addressed this issue and developed a microwave-promoted carbamoylation process based on the commonly used solvent dimethylformamide (DMF) as the carbon monoxide precursor75. Firstly, it was discovered that aryl dimethyl amides were accessible from the corresponding bromides in the presence of a nucleophilic catalyst, imidazole (Scheme 2.34). Secondly, tertiary benzamides other than dimethylamides were synthesised by addition of 3 equiv of an external amine (Scheme 2.34). 

The imidazole derivative, prochloraz, has a peculiar feature compared to the azole derivatives. The nitrogen atom in the 1-position of the imidazole is bonded to a carbamoyl group and not to alkyl. This compound, which is regarded as a tetrasubstituted urea, has a very broad spectrum and can be used in cereals both as a seed dressing and a foliar fungicide (9). 

Chemical Name methyl /V-( l-huiylcarbamoyl-2-benzimidazolc)carbamalc methyl l-(butyl-carbamoyl)benzimidazol-2-ylcarbamate methyl l - ( huiylaminojcarbonyl -1 //-benz-imidazol-2-ylcarbamate Uses as fungicide to control a wide range of diseases of fruit, nuts, vegetables, mushrooms, field crops, ornamentals, turf and trees also provides secondary acaricidal control, principally as an ovicide, etc. 

Another important intermediate in the preparation of 1,2-dihydropurines, 6-carbamoyl-and 6-cyanopurine derivatives is 5-amino-l-benzyl-4-[cyano(imino)methyl]imidazole (4). ... 

A two-step synthesis of 1,4-disubstituted imidazoles (8) from TOSMIC (1) plus an aldehyde, followed by reaction with ammonia or a primary amine, proceeds via a 4-tosyloxazoline (11). The reaction sequence could be classified as 1,2 and 1,5 bond formation, 1,5 bond formation, or transformation of another heterocycle. There are, however, analogies to the aldimine reactions, and so the process is detailed at this stage. Certainly the synthesis is carried out in two steps often with isolation of the oxazoline (see also Chapter 6). Heating (11) with a saturated solution of methanolic ammonia gives a 4-substituted imidazole with methanolic methylamine a 1,4-disubstituted product is isolated as a single regioisomer (Scheme 4.2.4). Some of the oxazolines cannot be isolated as they are unstable oils which have to be heated immediately with the amino compound [12]. Related is the synthesis of 2-carbamoyl-4-(2 -deoxy- 0-D-ribofuranosyl)imidazole [13]. 

AT-Aminopurines have been prepared from either pyrimidine or imidazole precursors. Thus 9-aminopurine may be obtained from 5-amino-4-hydrazinopyrimidine and formic acid (60JA4592). On the other hand 9-amino-8-methylhypoxanthine resulted from cyclization of l,5-diamino-4-carbamoyl-2-methylimidazole with triethyl orthoformate and acetic anhydride (61JCS4845). 

Thus, the appropriately substituted aniline or benzylamlne, prepared as shown, was treated with phosgene, and the resulting carbamoyl chloride reacted with Imidazole to give the product. 

An analogous reaction occurs with l-methyl-4-carbamoyI-5-aniino imidazole-2-thiol (XXXIVa, R=SH X=NCH3) and t-methyl-4-carbamoyl-5-aminoimidazole (XXXIVa, R = H X=NCH3) to give the corresponding purine derivatives listed in Table 9-... 

A-Glycosylimidazoles (related to nucleosides) are of interest in the preparation of novel chemotherapeutic agents, hence selective A -glycosylation techniques are of interest. The palladium-catalyzed addition of vinyl epoxides and allyl acetates to imidazoles provides one such route to imidazole nucleoside analogues <91JCS(Pi)2603, 9UOC4990>. The silyl-Hilbert-Johnson method is another in which the imidazole is silylated, then treated with a suitable peracetylated carbohydrate derivative in the presence of trimethylsilyl triflate catalyst. With 4-carbamoylimidazolium-5-olate, for example, the major product is the l-glycosyl-5-carbamoyl isomer with only low yields of the... 

Tosylmethylisocyanide (TOSMIC) has been used only rarely in syntheses of this type. One example though is the preparation of 2-carbamoyl-4-(2 -deoxy- -D-ribofuranosyl)imidazole from the deoxyribosylaldehyde <91TL6915>. 

Of the 1-carbamoyl imidazole derivatives The Boots Company found the compounds BTS 40 542 to be the most potent fungicide (Birchmore et al., 1977). The scheme of preparation of prochloraz is the following (Brookes et al.. 1973) ... 

CD-bonded stationary phases are suitable for the separation of positional, geometric and optical isomers, derivatives of dansyl racemic amino acids, analogues of nicotine and nicotine analogs, arbitrates and derivatives of benzodiazepin as well as organic nitrates, imidazol derivatives, etc. Table 8.2 shows that some enantioselective stationary phases are based on modified CDs [32,33]. The first CD derivatives used as a chiral stationary phase in HPLC were hydroxypropyl, acetylated and carbamoylated /3-CD, which demonstrated better selectivity behaviors than native /3-CD. The most common commercial species of CD derivatives include water-soluble methylated CD (2,6-di-0-methyl-j8-CD) and HP-j6-CD, then acetylated CD, carboxymethylated CD, naphthyl ethyl carbamate-j8-CD,... 

CAS 67747-09-5 68444-81-5 Synonyms 1 -N-Propyl-N-[2-(2,4,6-trichlorophenoxy) ethyl] carbamoyl imidazole... 

The chemistry and biochemistry of polyoxins has been discussed. The structure of the neopolyoxins A, B, and C, which are potent inhibitors of fungal cell-wall chitin synthetase, has been established neopolyoxins A and B are the imidazole nucleosides (18) and (19), respectively, whereas neopolyoxin C is the corresponding uracil-1-yl nucleoside the structure of polyoxin N was also revised, the amino-acid side-chain of (18) being replaced by 2-amino-5-(9-carbamoyl-2-deoxy-L-xyIonic acid. The new antibiotic nikkomycin B also has the structure of (18), although its stereochemistry has not been fully established. Adenomycin has... 

The commercially available and easily handled crystalline solid W,N -carbonyl-diimidazole (CDI) is utilized as a starting reagent for the general synthesis of unsymmetrical tetrasubstituted ureas. The intermediate carbamoyl imidazole 1017 is first obtained by reaction of CDI with a secondary amine. Compound 1017 is then converted into the more reactive and resonance-stabilized imidazolinium salt 1018 by N-alkylation of the imidazole moiety. Addition of a different secondary amine to 1018 furnishes N,N,N, N -unsymmetrical tetrasubstituted ureas 1019 in high yield (72-99%). 

The synthesis of an imidazole C-nucleoside linked through C-4, namely 2-carbamoyl-4-(2 -deoxy-j5-D-ribofuranosyl)imidazole 1586, was achieved by way of a nine-step reaction sequence starting from 2-deoxy-3,5-di-0-p-tolyl-D-erythro-pentofuranosyl chloride. The isocyanide intermediate 1585 was obtained by dehydration of the corresponding formamide 1584 with phosphoryl chloride, affording the imidazole 1586 in a good yield of 86% based on formamide 1584. Substituted imidazole nucleotides play a vital role in purine biosynthesis, and some of them... 

In 2002, Alterman and coworkers exploited this concept and developed a micro-wave-promoted carbamoylation protocol using DM F as the in situ carbon monoxide liberator in septum-sealed reaction vials [40]. It was discovered that aryl dimethyl amides were accessible from the corresponding bromides in the presence of KOt-Bu and the nucleophilic catalyst, imidazole (Scheme 4.27). Moreover, tertiary benza-mides other than dimethylamides were prepared by adding 3 equiv. of an external primary or secondary amine. This in situ carbon monoxide generation methodology... 

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