Aripiprazole → HCID 58579118, compound

HRID 2046149Notes

Reaction equation

HRID 2046149 reaction equation
[C:1](Cl)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[CH:8]1[CH:9]=[C:10]([N:16]2[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][CH2:24][CH2:25][O:26][C:27]3[CH:28]=[CH:29][C:30]4[CH2:37][CH2:36][C:34](=[O:35])[NH:33][C:31]=4[CH:32]=3)[CH2:18][CH2:17]2)[C:11]([Cl:15])=[C:12]([Cl:14])[CH:13]=1>N1C=CC=CC=1.C1C=C(N2CCN(CCCCOC3C=CC4CCC(=O)NC=4C=3)CC2)C(Cl)=C(Cl)C=1>[C:1]([O:35][C:34]1[CH2:36][CH2:37][C:30]2[C:31](=[CH:32][C:27]([O:26][CH2:25][CH2:24][CH2:23][CH2:22][N:19]3[CH2:20][CH2:21][N:16]([C:10]4[CH:9]=[CH:8][CH:13]=[C:12]([Cl:14])[C:11]=4[Cl:15])[CH2:17][CH2:18]3)=[CH:28][CH:29]=2)[N:33]=1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3]

Participants

5

Reactant 2

HCID 60795AripiprazoleHCID 62493Pivaloyl chloride

Product 1

HCID 58579118HCID 58579118, compoundYield 501.1%

Reagents, catalysts & solvents 2

HCID 60795AripiprazoleCatalystHCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of aripiprazole (0.1 g, 0.223 mmol) in pyridine (1 mL) at 0° C. was added pivaloyl chloride (0.055 mL, 0.446 mmol). After stirring at 0° C. for 5 minutes the reaction was allowed to warm to room temperature. After a further 5 minutes the temperature was increased to 50° C. for approximately 19 hours. The reaction was allowed to cool to room temperature. The reaction was repeated in a similar manner using of aripiprazole (1.75 g, 3.90 mmol). The two reaction mixtures were combined and quenched with approximately methanol (5 mL). The majority of the pyridine was removed in vacuo and the residue partitioned between dichloromethane (30 mL) and saturated NaHCO3 solution (30 mL). The aqueous phase was extracted with dichloromethane (2×30 mL) and the combined organic extracts washed with brine (20 mL) and dried over MgSO4. After filtration, the volatiles were removed (toluene and methanol/dichloromethane azeotrope) and the residue purified by silica chromatography eluting first with dichloromethane followed by ethyl acetate/dichloromethane/methanol (1:1:0.04) to give the title compound (1.19 g, 54%).

Workup

  1. temperatureto warm to room temperature
  2. temperatureAfter a further 5 minutes the temperature was increased to 50° C. for approximately 19 hours
  3. temperatureto cool to room temperature
  4. customThe two reaction mixtures
  5. customquenched with approximately methanol (5 mL)
  6. customThe majority of the pyridine was removed in vacuo
  7. customthe residue partitioned between dichloromethane (30 mL) and saturated NaHCO3 solution (30 mL)
  8. extractionThe aqueous phase was extracted with dichloromethane (2×30 mL)
  9. washthe combined organic extracts washed with brine (20 mL)
  10. dry with materialdried over MgSO4
  11. filtrationAfter filtration
  12. customthe volatiles were removed (toluene and methanol/dichloromethane azeotrope)
  13. customthe residue purified by silica chromatography
  14. washeluting first with dichloromethane

Sources & evidence

ORD record
ord-361f6c57127448ada7527941e8774a69
Source dataset
uspto-grants-2013_11
Patent number
US08592427B2

Reaction notes

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