Ethyl isocyanate → 7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-N-ethyl-3,4-dihydro-2-oxoquinoline-1(2H)-carboxamide

HRID 2046144Notes

Reaction equation

HRID 2046144 reaction equation
[CH:1]1[CH:2]=[C:3]([N:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][CH2:18][O:19][C:20]3[CH:21]=[CH:22][C:23]4[CH2:30][CH2:29][C:27](=[O:28])[NH:26][C:24]=4[CH:25]=3)[CH2:11][CH2:10]2)[C:4]([Cl:8])=[C:5]([Cl:7])[CH:6]=1.C(N(CC)CC)C.[CH2:38]([N:40]=[C:41]=[O:42])[CH3:39]>ClCCl>[Cl:8][C:4]1[C:5]([Cl:7])=[CH:6][CH:1]=[CH:2][C:3]=1[N:9]1[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][CH2:18][O:19][C:20]2[CH:25]=[C:24]3[C:23]([CH2:30][CH2:29][C:27](=[O:28])[N:26]3[C:41]([NH:40][CH2:38][CH3:39])=[O:42])=[CH:22][CH:21]=2)[CH2:11][CH2:10]1

Participants

5

Reactant 3

HCID 8022Ethyl isocyanateHCID 8471TriethylamineHCID 60795Aripiprazole

Product 1

HCID 565969547-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-N-ethyl-3,4-dihydro-2-oxoquinoline-1(2H)-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of aripiprazole (1.5 g, 3.35 mmol) in dichloromethane (33 mL) was added triethylamine (0.56 mL, 4.01 mmol) and ethyl isocyanate (0.53 mL, 6.69 mmol). The reaction was stirred at room temperature for 5 days. The reaction was quenched with water and extracted with dichloromethane (3×20 mL). The organics were combined, washed with saturated aqueous sodium hydrogen carbonate (20 mL) and brine (20 mL), dried over MgSO4 and concentrated. The product was purified by column chromatography on silica eluting with 0-3% methanol in 1:1 ethyl acetate to dichloromethane. The product was triturated in heptane to remove aliphatic impurities and then filtered and dried. The material was dissolved in ethyl acetate and washed with saturated aqueous sodium hydrogen carbonate (6×15 mL) to afford Compound-72 (0.482 g) as a pink solid.

Workup

  1. customThe reaction was quenched with water
  2. extractionextracted with dichloromethane (3×20 mL)
  3. washwashed with saturated aqueous sodium hydrogen carbonate (20 mL) and brine (20 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe product was purified by column chromatography on silica eluting with 0-3% methanol in 1:1 ethyl acetate to dichloromethane
  7. customThe product was triturated in heptane
  8. customto remove aliphatic impurities
  9. filtrationfiltered
  10. customdried
  11. dissolutionThe material was dissolved in ethyl acetate
  12. washwashed with saturated aqueous sodium hydrogen carbonate (6×15 mL)
  13. customto afford Compound-72 (0.482 g) as a pink solid

Sources & evidence

ORD record
ord-4331f1d37b35412d924b2784c793c8d2
Source dataset
uspto-grants-2013_11
Patent number
US08592427B2

Reaction notes

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