Diethyl Malonate → 5,7-Dichloro-3-nitro-4-hydroxy-1,2-dihydroquinolin-2-one
Reaction equation
[N+:1]([C:4]1[C:5](=[O:15])NC2C([C:13]=1[OH:14])=CC=CC=2)([O-:3])=[O:2].[Cl:16][C:17]1[CH:18]=[C:19]([CH:21]=[C:22]([Cl:24])[CH:23]=1)[NH2:20].C(OCC)(=O)CC(OCC)=O>>[Cl:16][C:17]1[CH:23]=[C:22]([Cl:24])[CH:21]=[C:19]2[C:18]=1[C:5]([OH:15])=[CH:4][C:13]([OH:14])=[N:20]2.[Cl:16][C:17]1[CH:23]=[C:22]([Cl:24])[CH:21]=[C:19]2[C:18]=1[C:5]([OH:15])=[C:4]([N+:1]([O-:3])=[O:2])[C:13](=[O:14])[NH:20]2Participants
Procedure
3-Nitro-4-hydroxy-1,2-dihydroquinolin-2-one 16a (Buckle, D. R., et al., J. Med. Chem. 18:726-732 (1975)) was prepared by nitration of 2,4-dihydroxyquinolin 15a (Scheme I, eq 6). Compound 16a was found to have a Ki value of 18 μM with a potency of 1.4% of 5,7-dichlorokynurenic acid (DCK). Further nitration of 16a gave mono-nitro subtituted compound 16b, which was found to be about as active as 16a. 5,7-Dichloro-2,4-dihydroxyquinoline 15c was prepared by reaction of 3,5-dichloroaniline with diethyl malonate followed by basic hydrolysis and cyclization in polyphosphoric acid (PPA) (eq 7). Patel, G. H., et al., J. Sci. Industr. Res. 19B:436-438 (1960). Nitration of 15c gave 5,7-dichloro-3-nitro-4-hydroxy-1,2-dihydroquinolin-2-one 16c which was found to have a Ki value of 1.4 μM with a potency of 19% of DCK. The binding ability of these nitro compounds to glycine/NMDA receptor is very similar to quinoxalinedione (QX) compounds (QX 2% of DCK, 5,7-dichloro-QX, 20% of QX). Thus, the series of 3-nitro-4-hydroxy-1,2-dihydroquinolin-2-ones provides some promising antagonists which bind to the glycine/NMDA receptor. ##STR15##
Sources & evidence
- ORD record
- ord-014c1348ddff4025b138b6c0b946632d
- Source dataset
- uspto-grants-1997_04
- Patent number
- US05622965
Reaction notes
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