Ethyl Acetate → HCID 58378949, compound

HRID 1951155Notes

Reaction equation

HRID 1951155 reaction equation
[CH3:1][C@H:2]1[CH2:7][NH:6][CH2:5][CH2:4][N:3]1[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].Cl[C:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:19]([C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)=[N:18][N:17]=1.C(N(C(C)C)CC)(C)C.CCOC(C)=O>CS(C)=O.O>[F:32][C:29]1[CH:28]=[CH:27][C:26]([C:19]2[C:20]3[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:16]([N:6]3[CH2:5][CH2:4][N:3]([C:8]([O:10][C:11]([CH3:13])([CH3:12])[CH3:14])=[O:9])[C@@H:2]([CH3:1])[CH2:7]3)=[N:17][N:18]=2)=[CH:31][CH:30]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 21152391-Chloro-4-(4-fluorophenyl)phthalazineHCID 10081508tert-Butyl (2S)-2-methylpiperazine-1-carboxylate

Product 1

HCID 58378949HCID 58378949, compoundYield 97.1%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
102 °C

Procedure

Add (S)-tert-butyl 2-methylpiperazine-1-carboxylate (276 g, 1.38 mol) to a slurry of 1-chloro-4-(4-fluorophenyl)phthalazine (275 g, 1.06 mol) and diisopropylethylamine (346 mL, 1.99 mol) in DMSO (2.56 L) at 25° C. Heat the mixture to 102° C. for 9 h. Cool the reaction to 25° C. and stir for 48 h. Add the mixture to EtOAc (2.5 L) and water (3.5 L). Extract the aqueous phase with ethyl acetate (2×2.0 L). Combine the organic layers, wash with water (2.5 L) and concentrate to a brown foam. Dissolve the foam in acetonitrile (1.0 L) and cool to 1° C. for 30 min. Filter the precipitate to obtain a tan solid. Concentrate the mother liquor and slurry the residue in acetonitrile (500 mL) for 30 min. Filter the mixture to obtain a tan solid. Combine the solid precipitates and dry in a vacuum oven (14 torr, 25° C.) for 25 h to obtain the title compound as a tan solid (435 g, 96%). ES/MS m/z 423.0 (M+1).

Workup

  1. temperatureCool
  2. customthe reaction to 25° C.
  3. extractionExtract the aqueous phase with ethyl acetate (2×2.0 L)
  4. washCombine the organic layers, wash with water (2.5 L)
  5. concentrationconcentrate to a brown foam
  6. dissolutionDissolve the foam in acetonitrile (1.0 L)
  7. temperaturecool to 1° C. for 30 min
  8. filtrationFilter the precipitate
  9. customto obtain a tan solid
  10. concentrationConcentrate the mother liquor
  11. customfor 30 min
  12. filtrationFilter the mixture
  13. customto obtain a tan solid
  14. customprecipitates
  15. customdry in a vacuum oven (14 torr, 25° C.) for 25 h

Sources & evidence

ORD record
ord-e685861948c1462280c39832497da77c
Source dataset
uspto-grants-2013_03
Patent number
US08404687B2

Reaction notes

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