Imidazole 2-butyl

At Merck Research Laboratories, the imidazole ring ia losartan (81, K = n — butyl), a novel clinical candidate against hypertension, was replaced with a pyrazole ring (52). Some of the best compounds are represented by formula (82), where K = n — butyl and R = 2,6-dichlorophenyl, 2-chlorophenyl, or... 

Imidazole, 4,5-dibromo-l-methyl-synthesis, S, 399 Imidazole, 4,5-di-t-butyl-synthesis, S, 483 X-ray diffraction, S, 350 Imidazole, 4,5-dichloro-chlorination, S, 398 synthesis, S, 398, 473 Imidazole, 4-(3,4-dichlorophenyl)-nitration, 5, 433 Imidazole, 4,5-dicyano-hydrolysis, S, 435-436 synthesis, S, 461, 472, 487 Imidazole, 4,5-dicyano-1-vinyl-synthesis, S, 387 Imidazole, 4,5-dihydro-mass spectra, 5, 360 Imidazole, 4-(dihydroxybutyl)-synthesis, S, 484 Imidazole, 4,5-diiodo-nitration, S, 396 synthesis, S, 400 Imidazole, 2,4-diiodo-5-methyl-iodination, S, 400 Imidazole, 1,2-dimethyl-anions... 

The BOC group has been introduced onto the imidazole nitrogen of histidine with BOCF (pH 7-8), BOCN3, MgO, and (B0C)20. ° It can be introduced onto pyrroles and indoles with phenyl /-butyl carbonate and NaH, 67-91% yield, or with NaH, BOCN3. ... 

In 2004, Alterman et al. used a microwave-assisted Ullmann-type protocol for the synthesis of N-(f-butyl)-3-[4-(lH-imidazol-l-yl)benzyl]-5-isobutylthiophene-2-sulfonamide (Scheme 106) [61]. Deprotection of the sulfonamide followed by carbamate formation via reaction with butyl chloro-formate finally gave the target compound for biological evaluation as selective angiotensin II AT2 receptor agonist. The IH-imidazole derivative, however, showed only a low affinity for the AT2 receptor (Ki value > 10 p,M). 

CN ( )-a-[[2 Butyl-l-[(4-carboxyphenyl)methyl]-17/-imidazol-5-yl]methylene]-2-thiophenepropanoicacid... 

CN 2-butyl-4-chloro-l-[[2 -(lH-tetrazol-5-yl)[l,r-biphenyl]-4-yl]methyl]-l//-imidazole-5-methanol monopotassium salt... 

C22H22C1N,0 114772-55-3) see Losartan potassium tert-butyl chloroformate (C5H9CIO2 24608-52-4) see Cefalexin 2-butyl-4-chloro-5-hydroxymethyiimidazole (CSII13CIN2O 79047-41-9) see Losartan potassium 2-butyl-4-cbloro-lif-imidazole-5-carboxaldehyde (CnHiiClNjO 83857-96-9) see Eprosartan Losartan potassium... 

C19H34N2O4 149550-86-7) see Eprosartan methyl 4-(acetylamino)-2-ethoxybenzoate (C12H15NO4 59-06-3) sec Mosapride citrate methyl acetylenecarboxylate (C4H4O2 922-67-8) see Rosoxacin methyl P-(acetyloxy)-2-butyl-l-[(4-carboxyphenyl)me-thyl]-a-(2-thienylmethyl)-l//-imidazole-S-propanoate (C2f,H3i)N20ftS) see Eprosartan... 

Gade and Bellemin-Laponnaz have reported the synthesis, in good yields, of chiral oxazoline-imidazoliums salts 10a (Scheme 8) obtained by reaction of 2-bromo-4(S)-t-butyl oxazoline with several mono-N-substituted imidazoles [16]. Similaly an imidazolium salt 10b bearing a paracyclophane substituent was prepared by Bolm [17]. 

Because esters 745 a, b of imidazole-acetic acid are unstable when stored for long periods, owing to intramolecular catalysis by the imidazole moiety, the esters should be converted into their salts or free acids and stored as such. Only tert-butyl imidazole-(4,5)acetates derived from tert-butyl 4-chloroacetoacetate seem to be stable [232, 233]. N-alkyl-substituted amidines give rise to a mixture of alkyl N-alkylimidazole-4- and 5-acetates [232, 233]. 

The tendency for N-nitrosamides to undergo hydrolysis by a nucleophilic catalysed pathway has been confirmed by studies of N-alkylnitroso acetamides (22) Results summarised in Table I for N -n-butyl-JJ -nitroso acetamide show that its decomposition is also subject to steric constraints (2,6-lutidinestrong nucleophiles (eg. imidazole, thiols) irrespective of their base strength (pK ). Further, the second order dependence on [Imidazole] is more clearly defined for the decomposit-... 

Scheme 3 Imidazole catalysed deamination of N-n-butyl-N-nitroso acetamide...

By adding one equivalent of alcohol to CDI at room temperature with or without base it is possible to isolate the imidazole-iV-carboxylate, which then reacts with a second mole of ROH to yield the carbonate. As in the case of alcoholysis of imidazolides, the reaction can be accelerated so effectively with catalytic amounts of NaOC2H5 or ImNa that it takes place in most cases exothermically, even at room temperature. However, tert-butyl alcohol, even when in excess, affords with CDI and base catalysis at room temperature only the imidazole-N-tert-butylcarboxylate, obviously for steric reasons. At higher temperature the carbonic ester is formed. Mixed carbonates such as ethyl benzyl carbonate or ethyl terf-butyl carbonate can be prepared with two different alcohols added sequentially.C9],[229]... 

In the reaction of an aminoalcohol with a methyl imidazole-AT-carboxylate or tert-butyl imidazole-AT-peroxycarboxylate, selective acylation of the amino function can be achieved11903 to give the carbamate and peroxycarbamate, respectively, the hydroxy groups of which can be further acylated ... 

A Lewis acid is also necessary for the acetylation of tetracarbonylferrate using N-acetylimidazole. In the absence of a Lewis acid, a Claisen-type condensation product was formed, which has been synthesized independently from 2 moles of A-acetylimidazole with sodium terf-butanolate in tert-butyl alcohol (55% yield) or with imidazole sodium in THF (95% yield) ... 

Table 16-1. Reduction of alcohols with tri- -butyl stannane via imidazole-Y-thionocarboxylates to the corresponding deoxygenated products.

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