5//-Imidazo isoindoles

Chemical Name 5-(4-chlorophenyl)-2,5-dihydro-3H-imidazo[2,1-a] isoindol-5-ol Common Name —... 

An intramolecular heteroaryl Heck was the pivotal step in the synthesis of 5-butyl-1-methyl-l//-imidazo[4,5-c]quinolin-4(5//)-one (63), a potent antiasthmatic agent [46], The optimum yield was obtained under Jeffery s ligand-free conditions, echoing Ohta s observation for the intermolecular version. Once again, the Caryi—Caryi bond was constructed at the C(5) position of the imidazole ring. Another intramolecular heteroaryl Heck cyclization of pyrrole and imidazole derivatives was also reported to assemble annulated isoindoles [47]. 

The imidazo[2,l-a]isoindole (234) has been prepared from 2-ethoxy-isoindole as shown in Eq. (29).311... 

Step 2 5-(p-Chlorophenyl)-5-Hydroxy-2,3-Dihydro-5H-Imidazo[2,l-a]Isoindole - l-(p-Chlorophenyl)-3-ethoxy-lH-isoindole (1 g), 2 g of ethyleneimine hydrotetrafluoroborate moistened with methylene chloride (containing approximately 0.66 g of dry salt) is refluxed in 25 ml of absolute toluene for 2 hours in an atmosphere of nitrogen. The resulting mixture is poured into 2 N sodium carbonate solution (25 ml) and extracted with ether. The ether solution is contacted with air for 6 days at room temperature to give the desired product. The crude material is recrystallized from acetone/hexane (1 1) to give 5-(p-chlorophenyl)-5-hydroxy-2,3-dihydro-5H-imidazo[2,l-a]isoindole MP 198° to 199°C. 

Radiosynthesis of5-[4-iodophenyl]-2,3-dihydro-5-hydroxy-5H-imidazo-[2,1-a]isoindole (309)... 

C f,H ClN20 6038-49-9) see Mazindol 9b-(4-chlorophcnyl)-l,2,3,9b-tctrahydro-l-[(4-mcthylphe-nyl)sulfonyl]-5//-imidazo 2,l-a]isoindol-5-one (C23H 9C1N20,S 22590-16-5) see Mazindol... 

In 1994, the synthesis of an isoindole derivative (236) was reported. It was achieved when 2,3-dihydro-7-nitro-l/f-imidazo[2. l-a]phthalazin-4-ium-6-olate (237) underwent a backbone rearrangement on treatment with dichloacetic anhydride <94H(38)1453>. 

Chlorophenyl)-2, 5-dihydro-3H-imidazo 2, 1-a isoindol-5-ol U.S.P. Mazanor (Wyeth) Sanorex (Sandoz)... 

Treatment of N-2,4-dinitrophenylpyridinium chloride (778) with phenyl-hydrazine in acetic acid causes reductive cyclization to yield the pyrido[l,2-ajimidazole (779). 3-Aminocrotononitrile, MeC(NH2)=CHCN, condenses with quinoline 1-oxide and isoquinoline 2-oxide to form the tricyclic compounds (780) and (781), respectively." The imidazo[5,l-a]isoquinoline derivative (783) is obtained by the action of phenyl isothiocyanate on the sodium salt of the Reissert compound (782)." ° Triethyl phosphite reduces the o-nitrophenyldipyr-rolylmethane (784 R=N02) to the nitrene (784 R = N), which forms the pyrrolo[3,2-6]quinoline derivative (785) by an intramolecular insertion reac-tion." 3-Amino-177-isoindole (786) reacts with acetylacetone in the presence of perchloric acid to yield the pyrimidoisoindolium salt (787). ... 

A soln. of 9b-p-chlorophenyl-l,2,3,9b-tetrahydro-5H-imidazo[2,l-a]-isoindol-5-one in tetrahydrofuran added dropwise during 10 min. at 15-25° under Ng to a stirred mixture of LiAlH4 and dry tetrahydrofuran, ca. 5 min. after addition is complete cooled to 10°, treated dropwise below 15° in turn with water, 15%-NaOH, and again water, and allowed to stand ca. 4 hrs. at room temp. -> 2-(2-aminoethyl)-3-(p-chlorophenyl)phthalimidine. Y 80%. P. Aeberli et al., J. Org. Chem. 40, 382 (1975). 

Non-Phenethylamlne Derivatives - The search continues for anorectic compounds not structurally related to phenethylamines. An isoindole derivative, 5-hydroxy-5-p-chloropheny1-2,3-dihydro-5H-Imidazo[2,1-a]-Isoindole, 42-548 (XIV) has been reported to have moderate anorexic effects in monkeys at doses below those producing significant CNS Stimulation.63 In obese male patients 42-548 was found to be an effective anorexigenic agent with no significant effects on sleep or mood. ... 

Ci bHi 7NO3, 1, 2,3,9b-Tetrahydro-9bp-hydroxy- 2/3-methoxy-1a-phenyl-5H-pyrrolO [2,1-a]isoindol-5 One, 46B, 277 ClbHigBrNjO, 1-Methyl-2-phenyl-5,10-dihydro-1H-imidazo[2,1-b]iso-quinolin-4-ium bromide monohydrate, 43B, 366 ClbHigBrN On, 4-Ethoxycarbonyl 5 p-bromooxoben20yl-8,8-dimethyl-3,4,9,1O-tetraazatricyclo[5.3.0.0 ]deca-2,9-diene, 40B, 275 CiBHigBr3N203, 11,12,13-Tribromo-3,6-diethyl-1O-ethoxycarbonyl-3,6-diazatricyclo[7.4.0.0 " ]trideca-2(7),9,11,13-tetraene-8-one, 46B, 277... 

The phosphoric acid having a 2,4,6-triisopropylphenyl moiety (223) has been found to be an effective catalyst for the intramolecular cascade imidization-nucleophilic addition-lactamisation reaction of methyl 2-formylbenzoates (220) with N -allqrlethane-1,2-diamines (221) (Scheme 59). Thus, medicinally interesting chiral 2,3-dihydro-lH-imidazo[2,l-a]isoindol-5(9Z>//)-ones (222) have been obtained with high yieids (89-94%) and excellent enantioselectivities (80-96% ee). ... 

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