Diisopropylethylamine → Benzamide

HRID 2199867Notes

Reaction equation

HRID 2199867 reaction equation
CO[C:3]1[CH:8]=[CH:7][C:6]([CH:9]([N:12](C)C)CN)=[CH:5][CH:4]=1.C([O:19]C1C(OC)=CC(C(O)=O)=CC=1OC)CCC.C(N(C(C)C)CC)(C)C.C[NH3+].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.F[P-](F)(F)(F)(F)F>CN(C=O)C>[C:9]([NH2:12])(=[O:19])[C:6]1[CH:7]=[CH:8][CH:3]=[CH:4][CH:5]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 4998377[2-Amino-1-(4-Methoxyphenyl)Ethyl]DimethylamineHCID 104450144-Butoxy-3,5-dimethoxybenzoic acidHCID 866211442-(1H-7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate Methanaminium

Product 1

HCID 2331Benzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

1-(4-methoxyphenyl)-N,N-dimethylethane-1,2-diamine represented by Formula 115 (134.6 mg, 0.69 mmol, purchased from Enamine Co.) was slowly added to 4-n-butoxy-3,5-dimethoxybenzoic acid represented by Formula 90 (193.8 mg, 0.76 mmol) prepared in Preparative Example 2 and diisopropylethylamine (0.48 mL, 2.77 mmol) in DMF (6 mL) at room temperature. After cooling the reaction mixture to 0° C. and adding 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate methanaminium (HATU, 289.76 mg, 0.76 mmol) thereto, the mixture was agitated at room temperature for 24 hours. The reaction solvent was removed under reduced pressure and chloroform (15 mL) was added to the remaining concentrate to prepare a solution. The solution was washed with a potassium carbonate solution, followed by separation to form an organic layer. After drying the organic layer with sodium sulfate (Na2SO4), the solvent was removed again under reduced pressure. The obtained vacuum-concentrated mixture was subjected to separation and purification through column chromatography (ethyl acetate/hexane/triethylamine, 2:1:0.1, v/v/v) using silica gel (SiO2), resulting in a benzamide compound represented by Formula 23 as a desired product (VVZ-024; 242.4 mg, 81% yield).

Workup

  1. customThe reaction solvent was removed under reduced pressure and chloroform (15 mL)
  2. additionwas added to the
  3. concentrationremaining concentrate
  4. customto prepare a solution
  5. washThe solution was washed with a potassium carbonate solution
  6. customfollowed by separation
  7. customto form an organic layer
  8. dry with materialAfter drying the organic layer with sodium sulfate (Na2SO4)
  9. customthe solvent was removed again under reduced pressure
  10. concentrationThe obtained vacuum-concentrated mixture
  11. customwas subjected to separation and purification through column chromatography (ethyl acetate/hexane/triethylamine, 2:1:0.1, v/v/v)

Sources & evidence

ORD record
ord-25bc6498186a42fca36c2dd4399d803c
Source dataset
uspto-grants-2016_06
Patent number
US09359346B2

Reaction notes

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