Diisopropylethylamine → Benzamide

HRID 2199872Notes

Reaction equation

HRID 2199872 reaction equation
O1CCN(C[CH:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[NH2:9])CC1.C([O:23]C1C(C)=CC(C(O)=O)=CC=1C)C1C=CC=CC=1.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:8]([NH2:9])(=[O:23])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27339934-Benzyloxy-3,5-dimethylbenzoic acidHCID 28144622-(Morpholin-4-yl)-1-phenylethan-1-amineHCID 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

2-morpholino-1-phenylethanamine represented by Formula 113 (38.4 mg, 0.186 mmol) was slowly added to 4-benzyloxy-3,5-dimethylbenzoic acid represented by Formula 144 (52.5 mg, 0.205 mmol, purchased from Medizin Co. Ltd.) and diisopropylethylamine (0.13 mL, 0.745 mmol) in DMF (3 mL) solution 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, 77.9 mg, 0.205 mmol) thereto, the mixture was agitated at room temperature for 24 hours. The reaction solvent was removed under reduced pressure and chloroform (2 mL) was added to the remaining concentrate to prepare a solution. The solution was washed with a potassium carbonate (K2CO3) 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 moved to a cartridge tube (6 mL, benzenesulfonic acid, 904030-WJ, UCT) using a small amount of ethyl acetate. Impurities were eliminated using methanol (15 mL) then separation and purification were conducted (using ethyl acetate/methanol/triethylamine, 20:2:1, v/v/v) to produce a benzamide compound represented by Formula 74 as a desired product (VVZ-080; 31 mg, 37% yield).

Workup

  1. customThe reaction solvent was removed under reduced pressure and chloroform (2 mL)
  2. additionwas added to the
  3. concentrationremaining concentrate
  4. customto prepare a solution
  5. washThe solution was washed with a potassium carbonate (K2CO3) 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 moved to a cartridge tube
  12. customseparation and purification

Sources & evidence

ORD record
ord-37892f21e7934721abc28b9832af2206
Source dataset
uspto-grants-2016_06
Patent number
US09359346B2

Reaction notes

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