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

HRID 656350Notes

Reaction equation

HRID 656350 reaction equation
P(Cl)(Cl)([Cl:3])=O.[NH2:6][C:7]1[C:12]([OH:13])=[CH:11][CH:10]=[CH:9][N:8]=1.[C:14]([CH:17]1[CH2:22][CH2:21]O[C:18]1=[O:19])(=O)[CH3:15].N>O>[OH:13][C:12]1[C:7]2=[N:6][C:14]([CH3:15])=[C:17]([CH2:22][CH2:21][Cl:3])[C:18](=[O:19])[N:8]2[CH:9]=[CH:10][CH:11]=1

Participants

6

Reactant 4

HCID 222AmmoniaHCID 106012-AcetylbutyrolactoneHCID 24813Phosphorus oxychlorideHCID 281142-Amino-3-Hydroxypyridine

Product 1

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

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a mixture comprising phosphorus oxychloride (2520 parts) and 2-amino-3-hydroxy pyridine (300 parts) was charged 2-acetyl butyrolactone (348 parts). The resulting mixture was heated to 60° to 65° C. and stirred for 10 hours at the same temperature. The reaction mass was cooled and poured into a mixture of ice and water to produce a quenched reaction mass. The pH was adjusted (pH meter) to 5.5 using aqueous ammonia. The resulting solid was filtered and washed with water followed by drying in vacuum oven to yield 235 parts of 9-hydroxy-3-(2-chloroethyl)-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one with a purity (HPLC) of 99%.

Workup

  1. temperatureThe resulting mixture was heated to 60° to 65° C.
  2. temperatureThe reaction mass was cooled
  3. customto produce
  4. customa quenched reaction mass
  5. filtrationThe resulting solid was filtered
  6. washwashed with water
  7. customby drying in vacuum oven

Sources & evidence

ORD record
ord-1a154ee9c0f841f080790c96f41ecd69
Source dataset
uspto-grants-2011_12
Patent number
US08071767B2

Reaction notes

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