Diisopropylamine → HCID 56596930, compound

HRID 2046143Notes

Reaction equation

HRID 2046143 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[CH:13]1[CH:14]=[C:15]([N:21]2[CH2:26][CH2:25][N:24]([CH2:27][CH2:28][CH2:29][CH2:30][O:31][C:32]3[CH:33]=[CH:34][C:35]4[CH2:42][CH2:41][C:39](=[O:40])[NH:38][C:36]=4[CH:37]=3)[CH2:23][CH2:22]2)[C:16]([Cl:20])=[C:17]([Cl:19])[CH:18]=1.[CH:43]([O:46][C:47](Cl)=[O:48])([CH3:45])[CH3:44]>CC1CCCO1>[Cl:20][C:16]1[C:17]([Cl:19])=[CH:18][CH:13]=[CH:14][C:15]=1[N:21]1[CH2:26][CH2:25][N:24]([CH2:27][CH2:28][CH2:29][CH2:30][O:31][C:32]2[CH:37]=[C:36]3[C:35]([CH2:42][CH2:41][C:39](=[O:40])[N:38]3[C:47]([O:46][CH:43]([CH3:45])[CH3:44])=[O:48])=[CH:34][CH:33]=2)[CH2:23][CH2:22]1

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 7917Isopropyl chloroformateHCID 60795AripiprazoleHCID 178418339Butyllithium

Product 1

HCID 56596930HCID 56596930, compound

Reagents, catalysts & solvents 1

HCID 73012-MethyltetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of diisopropylamine (1.11 mL, 7.87 mmol) in 2-methyltetrahydrofuran (37 mL) at −5° C. was added n-BuLi (3.0 mL, 2.5 M in hexanes, 7.49 mmol) slowly. After 20 minutes, the reaction was cooled to −78° C. and Aripiprazole (1.68 g, 3.74 mmol) was added. After a further 10 minutes, isopropylchloroformate (9.37 mL, 1.0 mol in toluene, 9.37 mmol) was added. The reaction was held at −78° C. for 2 hours before allowing to warm to room temperature overnight. The reaction was quenched with saturated aqueous ammonium chloride solution (30 mL) and extracted with ethyl acetate (2×30 mL). The organics were combined, washed with saturated aqueous sodium hydrogen carbonate solution (30 mL), brine (30 mL), dried over MgSO4 and concentrated. The crude product was purified by column chromatography on silica eluting with 1:1 ethyl acetate to dichloromethane to 2% methanol in 1:1 ethyl acetate to dichloromethane to give the product. The product was recrystallized from isopropanol to remove aliphatic impurities. The product was not sufficiently pure so was purified by column chromatography eluting with 0 to 10% tetrahydrofuran in ethyl acetate. The product was triturated in heptane and filtered to afford Compound-75 (0.593 g) as a colorless solid.

Workup

  1. waitAfter a further 10 minutes
  2. waitThe reaction was held at −78° C. for 2 hours
  3. temperatureto warm to room temperature overnight
  4. customThe reaction was quenched with saturated aqueous ammonium chloride solution (30 mL)
  5. extractionextracted with ethyl acetate (2×30 mL)
  6. washwashed with saturated aqueous sodium hydrogen carbonate solution (30 mL), brine (30 mL)
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customThe crude product was purified by column chromatography on silica eluting with 1:1 ethyl acetate to dichloromethane to 2% methanol in 1:1 ethyl acetate to dichloromethane
  10. customto give the product
  11. customThe product was recrystallized from isopropanol
  12. customto remove aliphatic impurities
  13. customwas purified by column chromatography
  14. washeluting with 0 to 10% tetrahydrofuran in ethyl acetate
  15. customThe product was triturated in heptane
  16. filtrationfiltered
  17. customto afford Compound-75 (0.593 g) as a colorless solid

Sources & evidence

ORD record
ord-29e8bb7f3cbd42b297f52857c91f3eec
Source dataset
uspto-grants-2013_11
Patent number
US08592427B2

Reaction notes

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