Thionyl Chloride → 3-(2-Chloroethyl)-2-methyl-9-hydroxy-4H-pyrido[1,2-a]pyrimidin-4-one (Paliperidone)

HRID 656349Notes

Reaction equation

HRID 656349 reaction equation
[OH:1][C:2]1[C:7]2=[N:8][C:9]([CH3:16])=[C:10]([CH2:13][CH2:14]O)[C:11](=[O:12])[N:6]2[CH:5]=[CH:4][CH:3]=1.S(Cl)([Cl:19])=O>CN(C)C=O>[OH:1][C:2]1[C:7]2=[N:8][C:9]([CH3:16])=[C:10]([CH2:13][CH2:14][Cl:19])[C:11](=[O:12])[N:6]2[CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 24386Thionyl ChlorideHCID 166560309-Hydroxy-3-(2-hydroxyethyl)-2-methylpyrido[1,2-a]pyrimidin-4-one

Product 1

HCID 248985163-(2-Chloroethyl)-2-methyl-9-hydroxy-4H-pyrido[1,2-a]pyrimidin-4-one (Paliperidone)

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

According to the U.S. Pat. No. 5,688,799 (hereinafter referred to as the '799 patent), the compound of formula I is prepared by the reaction of 2-amino-3-hydroxypyridine with 2-acetylbutyrolactone in the presence of p-toluenesulfonic acid in xylene solvent at reflux temperature for overnight using a water separator to yield 9-hydroxy-3-(2-hydroxyethyl)-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one. The 9-hydroxy-3-(2-hydroxyethyl)-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one is converted into its hydrochloride salt, followed by reaction with thionyl chloride in dimethylformamide to produce 9-hydroxy-3-(2-chloroethyl)-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one.

Sources & evidence

ORD record
ord-3ec2d7f5aadd4b208d85f20773475711
Source dataset
uspto-grants-2011_12
Patent number
US08071767B2

Reaction notes

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