37/-Pyrrolo imidazole

Diaza-compounds. The pyrrolo-pyrazole derivative (705) is one of the products of the action of acids on the tosylhydrazone H2C=CMe(CH2)2CH=N—NHTos. The reaction of 2,5,5-trimethyl-l-pyr-roline iV-oxide (706) with the ketenimine Ph2C=C=NPh yields the pyrrolo-imidazole (707)/ Pyrazolidin-3-one and 3-chloropropanoyl chloride combine to form the dioxopyrazolopyrazole (708)/ Irradiation of l-(o-iodoben-zoyl)imidazole (709 R=H) produces the indolobenzimidazolinone (710) the... 

Addition to Tetrahydro-2//-l,3-oxazines, Hexahvdro-1 f/-pyrrolo[l,2-r]imidazoles and... 

Besides high effectiveness in the diastereoselective control of nucleophilic addition reactions, another major goal in the design of chiral auxiliaries is the use of readily available, chiral starting materials. The hexahydro-l//-pyrrolo[l,2-c]imidazole derivatives 9a-e are examples which use the inexpensive amino acid L-proline (7) as starting material. 

By condensation of 1-acetylimidazole or l-(l-pentin-4-oyl)imidazole with dimethyla-cetyl-enedicarboxylate at higher temperature, 7/f-pyrrolo[l, 2-a]imidazoles are formed along with dimethyl(imidazol-l-yl)fumarate tl58],[157]... 

Reaction of 108 with dimethyl acetylenedicarboxylate gave pyrrolo[2,3-4] imidazole 111 in poor yield (Equation 11) <2001JHC205>. 

Dihydro-l//-pyrrolo[ 1,2-c]imidazoles are also known, particularly in the dioxo series <1998JME63, 2004JOC9313> and 5,6,7,7a-tetrahydropyrrolo- <2005JOC2368>. One example of the 5,6,7,7a-tctrahydropyrrolo[ 1,2-c] imidazolidi-num salt is described <2005CEJ1833>. 

Pyrrolo[l,2- ]imidazoles are mainly present in the literature as perhydro derivatives. Some of these substituted compounds present interesting biological activity. The aromatic unsaturated system is rare and was prepared in one case by flash vacuum pyrolysis <1999J(P1)2047>. 

Some structures, related to pyrrolo[l,2- ]imidazoles, have been reported. The tricyclic perhydro derivative 49 <1997TL1647> as well as the 3-( 1 //-indol-3-ylmethy 1 )-7a-methyldihydro-1-phenylamino-l//-pyrrolo[ 1,2-tf] imidazole-2,5(3//,6//) dione 50 have been determined and some interesting aspects on compound 50 have been highlighted. 

Treatment of methylhexahydro-l//-pyrrolo[l,2- ]imidazole 60a with LiAlH4 in Et20 afforded a diol 61a in 87% yield, whereas similar treatment of 60b gave alcohol 61b in 98% yield. During the reduction, no ring opening was observed (Equation 7) <1998J(P1)2061>. 

A diastereoselective dipolar cycloaddition of chiral nitrone 80 with alkene dipolarophiles afforded imidazo[ 1,2-3]-isoaxazole (Scheme 9). The conversion via N-O reduction of this ring system with Raney-Ni in methanol gave the corresponding pyrrolo[l,2-A imidazole in 66% yield. The structure has been confirmed by X-ray diffraction crystal stmcture analysis <2000SL967>. 

Several pyrrolo[l,2-f] imidazoles have been studied for their physiological activities. Most of these compounds demonstrated a high affinity for the 5-HT1A receptor. Pyrrolo[l,2-o]imidazoles are present in the literature as tetrahydro, perhydro, 1-oxoperhydro, 3-oxoperhydro, 7-oxoperhydro, 1,3-dioxoperhydro, 1,5-dioxoperhydro, 2,7-dioxoperhydro, and 1 -thio-3-oxoperhydro derivatives. 

Table 1 Preparation of various dihydro-1 H-pyrrolo[1,2-a]imidazole-2,5-diones...

The reaction of nitrone 99 with dimethyl acetylenedicarboxylate (DMAD) at room temperature in CH2CI2 gave a colorless crystalline product that has been identified as trimethyl 3,3-dimethyl-l-phenyl-377-pyrrolo[l,2-f]imidazole-5,6,7-tricarboxylate 100. A mechanism explaining this transformation has been reported (Equation 13) <2001RCB882>. 

The aziridine 101 derived from pyrrole-2-carboxaldehyde was found to undergo a further unusual transformation when treated with trifluoroacetic acid (TFA) at room temperature, giving the 5//-pyrrolo[l,2-r ]imidazole 102 in good yield. The cyclization is initiated by protonation of the carbonyl group (Scheme 10) <2000TL4991>. 

A synthesis of 5//-pyrrolo[l,2-r] imidazole 105 has been developed via a chemoselective addition/dehydration of acetaldehyde on diiodo imidazole 103 giving the vinylic imidazole 104. This compound, treated under the metathesis condition in the presence of the second-generation Grubbs catalyst, gave the final product 105 (Scheme 11) <2003TL1379>. 

A parallel library of optically active bicyclic tertiary amines 127 bearing N-chiral bridgehead nitrogen atoms was readily prepared by condensation of primary amines, cyclic amino acids 126, and aldehydes. This method gives access to a large variety of substituted hexahydro-l/7-pyrrolo[l,2-/ ]imidazol-l-ones of type 127 (Scheme 16). These... 

A synthesis of l,3-pyrrolo[l,2-f]imidazoles 148 has been obtained by reacting 147 with isocyanates in THF under reflux for 4h in the presence of DBU. This reaction gave high yields of l,3-dioxo-l,2,3,4-tetrahydropyrrolo[l,2-f]-imidazoles (Equation 20) <2004JOC9313>. 

A related series of diaryl pyrrolo[l,2-a]imidazoles, represented by SK F 104351 (149), 104493 (150) and 105809 (151), has been reported to show similar profiles [360,366]. In mice and rats, SK F 105809 was a prodrug for the active methyl sulphide SK F 105561 (152), which was about 10-fold more potent in vitro than SK F 86002 [367]. The in vivo profile of SK F 105809, which is reported to be in clinical trials, was similar to that of SK F 86002. 

The nitrogen rr-electron analogue of indolizine, pyrrolo[l,2-a]-imidazole [180], shows more complicated protonation behaviour... 

Alekseeva et al. (1972b) have carried out a comparison of calculated values of localization energies and free valency indices of pyrrolo[ 1,2-a] imidazole, pyrrolo[l,2-a] benzimidazole and indolizine. In all these molecules the a-position of the pyrrole ring is calculated to be more reactive than the / -position. The free valence indices increase in the order indolizine < pyrrolobenzimidazole < pyrroloimidazole, which is also the order of increasing basicity. 

Variation of the ring portion of acyclovir has been achieved. Compounds include monocyclic (isocytosine, triazole, imidazole), bicyclic (adenine, 8-azapurine, pyrrolo[2,3-c/]-pyrimidine, pyrazolo[3,4-[Pg.131]

Fusion of the imidazole ring to pyrrolo-benzothiadiazepine 340 can be achieved by straightforward TosMIC cycloaddition approach (Scheme 72, Section 4.2 (1994JHC1033)). An alternative sequence starts with the addition of nitromethane to the C-N double bond on the thiadiazepine ring, nitro group reduction and manganese oxide oxidation of the intermediate dihydroimidazole derived from amine 342 and tiiethyl ortho formate. 

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