Succinic anhydride → HCID 53232556, compound

HRID 1055262Notes

Reaction equation

HRID 1055262 reaction equation
[CH3:1][C:2]1[N:12]=[C:11]2[N:6]([CH2:7][CH2:8][CH2:9][CH:10]2[OH:13])[C:4](=[O:5])[C:3]=1[CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][CH:19]([C:22]2[C:23]3[CH:24]=[CH:25][C:26]([F:31])=[CH:27][C:28]=3[O:29][N:30]=2)[CH2:18][CH2:17]1.[C:32]1(=[O:38])[O:37][C:35](=[O:36])[CH2:34][CH2:33]1>N1C=CC=CC=1.CN(C)C1C=CN=CC=1>[F:31][C:26]1[CH:25]=[CH:24][C:23]2[C:22]([CH:19]3[CH2:20][CH2:21][N:16]([CH2:15][CH2:14][C:3]4[C:4](=[O:5])[N:6]5[CH2:7][CH2:8][CH2:9][CH:10]([O:13][C:32](=[O:38])[CH2:33][CH2:34][C:35]([OH:37])=[O:36])[C:11]5=[N:12][C:2]=4[CH3:1])[CH2:17][CH2:18]3)=[N:30][O:29][C:28]=2[CH:27]=1

Participants

5

Reactant 2

HCID 7922Succinic anhydrideHCID 115237Paliperidone

Product 1

HCID 53232556HCID 53232556, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Conditions

Temperature
60 °C

Procedure

Paliperidone (10 g, 23.45 mmol) was dissolved in pyridine (100 mL) together with N,N-dimethyl-4-pyridinamine (0.5 g; 4.09 mmol) and succinic anhydride (18.3 g; 182.86 mmol). The mixture was stirred under an argon atmosphere for 4 h at 60° C. and for 48 h at room temperature. The reaction mixture was evaporated and dissolved in dichloromethane/methanol (100 mL/10 mL) and water (100 mL). The aqueous phase was extracted five times with dichloromethane/methanol (100 mL/10 mL). The organic layers were combined, dried over Na2SO4 and evaporated under vacuum. The residue was purified by silica gel chromatography (gradient elution with chloroform/ethanol 80/20 to 70/30). The product was dissolved in isopropanol (50 mL) and the resulting precipitate was filtered and washed with isopropanol (10 mL). The precipitate was dried in vacuo to give the title compound as a white solid. ESI-MS (M+1) 528. 1H NMR: (DMSO-d6, 360 MHz): δ ppm 1.75-2.75 (m, 23H), δ 3.5-4.0 (m, 3H), δ 5.74 (m, 1H), δ 7.28 (td, J=9.15, 2.20 Hz, 1H), δ 7.69 (dd, J=8.96, 2.01 Hz, 1H), δ 8.02 (dd, J=8.78, 5.12 Hz, 1H).

Workup

  1. customThe reaction mixture was evaporated
  2. dissolutiondissolved in dichloromethane/methanol (100 mL/10 mL)
  3. extractionThe aqueous phase was extracted five times with dichloromethane/methanol (100 mL/10 mL)
  4. dry with materialdried over Na2SO4
  5. customevaporated under vacuum
  6. customThe residue was purified by silica gel chromatography (gradient elution with chloroform/ethanol 80/20 to 70/30)
  7. dissolutionThe product was dissolved in isopropanol (50 mL)
  8. filtrationthe resulting precipitate was filtered
  9. washwashed with isopropanol (10 mL)
  10. customThe precipitate was dried in vacuo

Sources & evidence

ORD record
ord-31879e2cf96944c59fa9699eb60ff9e5
Source dataset
uspto-grants-2016_07
Patent number
US09394354B2

Reaction notes

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