Benzyl urea

A -(Aza)naphthyl-V -aryl(benzyl)ureas V-Aryl-Y-Alkylaminocarbonyl Ethylendiamines N, V -Dibenzylthioureas... 

The application of the naphthalene-catalyzed (10%) lithiation to benzylic ureas 69 under Barbier-type conditions in THF at —78 or — 30°C led to the formation of the expected products 35, after hydrolysis (Scheme 28) °. 

The hydantoins (116 and 117) have been prepared from DL-j8-ferrocenyl-a-alanine and N - ferrocenyl methyl-AT-(a-carbethoxy-benzyl)urea, respectively.68 The Friedel Crafts reaction of ferrocene and 2-pyrroylchloride gave the ketone (118).112,113 The polarographic half-wave potentials of 118 and other related ferrocenes were measured113 and it was concluded that the ferrocene radical was more electropositive than the phenyl radical. 

The azepinyl and 1,4-diazepinyl (homopiperazine) moieties were frequently reported in 2007 by medicinal chemistry groups for exploration of SAR around cyclic amino or cyclic diamino residues, respectively. Examples where the azepinyl substituent yielded optimal activity include l-(aryl)-3-(4-(amino)benzyl)urea transient receptor potential vanilloid 1 antagonists <07JMC3651> the 1,4-diazepinyl-substituent yielded optimal activity for anthranilimide derivatives as potent inhibitors of factor Xa and displayed in vitro... 

Yield given based on benzyl urea tosylate, the precursor for 3-(benzyloxy)-3-chlorodiazirine. 

Pfizer patented a series of AR ligands which are analogs of the Ligand Pharmaceuticals 6-quinolinone templates. These AR ligands are of three templates (i) 6-sulfonamide pyridones [132], (ii) benzyl urea pyridones [133] and (iii) benzyl coumarins [134] that appear to be weak affinity (micromolar) antagonists which are illustrated as representative examples 41, 42 and 43, respectively, in Figure 8.10. Conspicuously absent from these quinolinones is the aniline moiety, which may explain the low affinity and lack of agonist activity. 

Among many naturally occurring compounds, such as tetrodotoxin, the guanidi-nium group plays an important role in expressing biological activity due to its cationic nature. It can be direcdy prepared from trichloroacetamide 1709 via allyl benzyl urea 1710 by dehydration with triphenylphosphine/tetrabromomethane and triethylamine at room temperature or —20 °C affording carbodiimide 1711 in 99%... 

Thiourea, unlike urea, readily reacts in the tautomeric form (I) in the presence of suitable reagents, particularly alkyl halides thus benzyl chloride reacts with... 

When the aromatic aldehyde is omitted from a Biginelli reaction mixture, a dihydropyrimidine is still formed. Thus, for example, phenylacetaldehyde (2 mol) and urea (1 mol) react to give 4-benzyl-5-phenyl-3,4-dihydropyrimidin-2(li/)-one (676) (33JA3361). 

Condensation of 165 with ethoxymethylenemalononitrile gave 171, and with ethyl ethoxymethylenecyanoacetate or methyl bis(methylmercapto)-methylene cyanoacetate it yielded 172 (80AP108). The reaction of 172 with urea, thiourea, and benzyl nitrile afforded 173 (91PHA98). Treatment of hydrazino derivatives 165 with alkyl, aryl, or aralkyl isothiocyanates yielded (86JHC1731) 3-(/V-substituted-thiocarbamoyl)-hydrazino[l,2,4]triazino[5,6-b]indoles which have been evaluated for in vitro antimicrobial activity (Scheme 36). 

Condensation (Continued) of ethyl matonate with urea, 18, 8 of ethyl oxalate with acetone, 17, 40 of ethyl oxalate with benzyl cyanide, 11,40... 

The benzyl phosphonate triesters 100 reacted with isocyanates under similar conditions to give the corresponding cyclic urea phosphonate diesters 101 (2). 

Jacobsen and co-workers also described the highly enantioselective hydrocyanation of ketimines with the urea analogue. After recrystallisation of the corresponding Strecker adduct, formylation and hydrolysis, the N-benzyl R-methylphenylglycine, was obtained. The R-amino acid hydrochloride is obtained in 93% overall yield with > 99.9% ee on a gram scale [149]. 

The last reaction perhaps involves an intermediate such as 33a which expells a proton and dimethyl sulfide. Formation of the Schiff s base with t-butylamine, reduction with sodium borohydride and hydrogenolysis of the benzyl ether produces sulfonterol (28). Despite the fact that the methylene hydrogen of sulfonterol must be much less acidic than of the corresponding urea proton on carbuterol or the sulfonamide proton on soterenol, good bioactivity is retained. 

The immobilized carbamates (40 pmol) were transferred to a sealable 96-well Weflon plate, and admixed with 10 pmol each of various primary or secondary amines dissolved in 400 iL of anhydrous toluene. After sealing, the plate was irradiated in a multimode microwave instrument, first generating a ramp to reach 130 °C within 45 min and then holding this temperature for an additional 15 min. After cooling, the resins were filtered with the aid of a liquid handler and the filtrates were concentrated to obtain the desired substituted ureas in good purity and reasonable yields. Anilines reacted rather sluggishly and 2-substituted benzyl carbamates afforded somewhat inferior results. 

The reaction of pentafluorophenyl isocyanate with thiadiazole 8 in acetonitrile at room temperature gave 5-penta-fluorophenylureido-l,3,4-thiadiazole-2-sulfonamide 105 (Equation 31) <2004JME2796>. Similarly, 2-amino-l,3,4-thia-diazole 37 reacts with benzyl isocyanate in dry THF to afford the l,3,4-thiadiazol-2-yl urea 106 in 94% yield (Equation 32) <1999JME1525>. 

In contrast to the Michaelis-Arbuzov reaction, triaryl phosphites prove to be quite useful for addition to a,(3-unsaturated carbonyl compounds in this type of reaction. A wide variety of unsaturated compounds have been utilized successfully as substrates for such additions, including condensation products of the simple carbonyl compounds with urea,229 thiourea,230-233 N-substituted thioureas,232 234 235 ethyl carbamate,236 2-imidazolidinone,237 2-imidazoli-dinethione,237 and benzyl carbamate.238-240... 

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