1-(2-Chloroethyl)imidazolidin-2-one → Sertindole

HRID 1250030Notes

Reaction equation

HRID 1250030 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1)[CH:6]=[C:5]2[C:18]1[CH2:19][CH2:20][NH:21][CH2:22][CH:23]=1.Cl[CH2:25][CH2:26][N:27]1[CH2:31][CH2:30][NH:29][C:28]1=[O:32]>>[CH:12]1[C:11]([N:7]2[C:8]3[CH:9]=[CH:10][C:2]([Cl:1])=[CH:3][C:4]=3[C:5]([CH:18]3[CH2:19][CH2:20][N:21]([CH2:25][CH2:26][N:27]4[C:28](=[O:32])[NH:29][CH2:30][CH2:31]4)[CH2:22][CH2:23]3)=[CH:6]2)=[CH:16][CH:15]=[C:14]([F:17])[CH:13]=1

Participants

3

Reactant 2

HCID 754351-(2-Chloroethyl)imidazolidin-2-oneHCID 98838385-Chloro-1-(4-fluorophenyl)-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole

Product 1

HCID 60149Sertindole

Procedure

The intermediate may be worked up in a conventional manner. The further process leading to sertindole comprises cyclization of N-(4-fluorophenyl)-N-(2-carboxy-4-chlorophenyl)glycine to the corresponding 3-acetoxy-indole using eg. acetic anhydride in the presence of alkalimetal acetate such as sodium acetate. 5-chloro-1-(4-fluoro)indole is then obtained from the 3-acetoxy-indole by reduction and subsequent elimination of H2O. The resulting 5-chloro-1-(4-fluorophenyl)indole is reacted with 4-piperidone according to the above procedure, the resulting 5-chloro-1-(4-fluorophenyl)-3-(1,2,3,6-tetrahydropyridin-4-yl)indole is reduced in order to obtain 5-chloro-1-(4-fluorophenyl)-3-(piperidin-4-yl)indole which in turn is reacted with 1-(2-chloroethyl)-2-imidazolidinon to obtain sertindole. Alternatively, the 5-chloro-1-(4-fluorophenyl)-3-(1,2,3,6-tetrahydropyridin-4-yl)indole may first be reacted with 1-(2-chloroethyl)-2-imidazolidinon followed by reduction, thereby obtaining sertindole, which may be isolated as an acid addition salt, e.g. the tartrate, or as the free base.

Sources & evidence

ORD record
ord-2eb8cc3c1125421095c49012257440de
Source dataset
uspto-grants-2002_01
Patent number
US06335463B1

Reaction notes

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