HCID 13590325, compound → HCID 13590326, compound

HRID 1380098Notes

Reaction equation

[Cl:1][C:2]1[C:10]([Cl:11])=[C:9]2[C:5]([CH2:6][C:7]([CH:14]3[CH2:18][CH2:17][CH2:16][CH2:15]3)([CH3:13])[C:8]2=[O:12])=[CH:4][C:3]=1[NH:19]CCO.CC(C)=O.OS(O)(=O)=O.O=[Cr](=O)=O>>[NH2:19][C:3]1[CH:4]=[C:5]2[C:9](=[C:10]([Cl:11])[C:2]=1[Cl:1])[C:8](=[O:12])[C:7]([CH:14]1[CH2:15][CH2:16][CH2:17][CH2:18]1)([CH3:13])[CH2:6]2

Participants

Reactant 2

HCID 13590325HCID 13590325, compound

HCID 131709961Jones' reagent

Product 1

HCID 13590326HCID 13590326, compound

Procedure

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##

Sources & evidence

ORD record: ord-151d5ebf242d4f3193ecd15f5c1df252
Source dataset: uspto-grants-1986_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04579869

Reaction notes

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