HCID 13590325, compound → HCID 13590326, compound

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Reaction Steps

The starting material 2,3-dichloro-2-cyclopentyl-2,3-dihydro-5-hydroxy-2-methyl-1H-inden-1-one is alkylated with ethylene bromide in the presence of potassium carbonate to form 5(2-bromoethoxy)-6,7-dichloro-2-cyclopentyl-2,3-dihydro-2-methyl-1H-inden-1-one (Step 1). This material is then reacted with liquid ammonia to accomplish the substitution of bromine by ammonia and to form 6,7-dichloro-2-cyclopentyl-2,3-dihydro-5-(2-aminoethoxy)-2-methyl-1H-inden-1-one (Step 2). Following the formation of the compound of Step 2, an intramolecular Smiles rearrangement takes place (Step 3). The 6,7-dichloro-2-cyclopentyl-2,3-dihydro-5-(2-hydroxyethylamino)2-methyl-1H-inden-1-one formed in Step 3 is then oxidized with Jones Reagent (CrO3, H2SO4, H2O) to form 5-amino-6,7-dichloro-2-cyclopentyl2,3-dihydro-2-methyl-1H-inden-1-one (Step 4). When n is 1, 3 or 4, alkylation of the amino group (Step 5) with a haloalkanoic acid ester, such as ethyl bromoacetate, followed by acid or base hydrolysis of the alkyl ester (Step 6) gives a compound of the present invention, such as [6,7-dichloro-2-cyclopentyl-2,3-dihydro-2-methyl-1-oxo-1H-inden-5-yl)amino]acetic acid. When n is 3, alkylation with 4-bromo-1-butene followed by oxidation with potassium permanganate gives the compound of the present invention, without the need for hydrolysis. The starting material used in these examples is obtained as shown in Woltersdorf, O. W. et al., J. Med. Chem., 20, 1400 (1977). This synthetic route is illustrated ##STR3##

Provenance & Evidence