1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Ethyl 3-{[2-(4-morpholinyl)ethyl]oxy}benzoate

HRID 251382

Reaction equation

HRID 251382 reaction equation
NC1N([C:7]2[CH:8]=[C:9]([CH:13]=[CH:14][C:15]=2C)[C:10]([OH:12])=[O:11])N=CC=1C(=O)C1C=CC=CC=1.[C:25]([O:29][C:30](=O)NN)([CH3:28])(C)C.CCN=C=NC[CH2:40][CH2:41][N:42]([CH3:44])C.[CH:45]1C=CC2N(O)N=NC=2[CH:50]=1.[Cl-].[Na+].[OH2:57]>CN(C=O)C>[CH2:45]([O:12][C:10](=[O:11])[C:9]1[CH:13]=[CH:14][CH:15]=[C:7]([O:57][CH2:40][CH2:41][N:42]2[CH2:28][CH2:25][O:29][CH2:30][CH2:44]2)[CH:8]=1)[CH3:50]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 70091tert-Butyl carbazateHCID 757711-HydroxybenzotriazoleHCID 112094383-(5-amino-4-benzoyl-1H-pyrazol-1-yl)-4-methylbenzoic acidHCID 57417360Sodium chloride; water

Product 1

HCID 58089039Ethyl 3-{[2-(4-morpholinyl)ethyl]oxy}benzoateYield 26%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To DMF (10 mL) at rt was added 3-(5-amino-4-benzoyl-pyrazol-1-yl)-4-methyl-benzoic acid 1 (0.50 g, 1.56 mmol, 1.0 eq), t-butylcarbazate (0.206 g, 1.56 mmol, 1.0 eq), EDCI (0.313 g, 1.63 mmol, 1.05 eq) and HOBt (0.238 g, 1.56 mmol, 1.0 eq). The reaction was stirred for 19 h, poured into brine (100 mL) and extracted with EtOAc (2×20 mL). The organic extracts were combined were washed with brine (1×20 mL). The brine layer was separated and extacted with EtOAc (1×10 mL). All organic extracts were combined dried over Na2SO4, filtered and concentrated in vacuo. This material was dissolved in CH2Cl2 (10 mL) and cooled to 0° C. TFA (3 mL) was added and the reaction mixture allowed to warm to rt over 2 h. The solvent was removed in vacuo to give crude solid which was triturated with EtOAc/ether (1/1) giving 2 (180 mg, 26%)as a light tan in color solid.

Workup

  1. extractionextracted with EtOAc (2×20 mL)
  2. washThe organic extracts were combined were washed with brine (1×20 mL)
  3. customThe brine layer was separated
  4. dry with materialAll organic extracts were combined dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThis material was dissolved in CH2Cl2 (10 mL)
  8. additionTFA (3 mL) was added
  9. temperatureto warm to rt over 2 h
  10. customThe solvent was removed in vacuo
  11. customto give crude solid which
  12. customwas triturated with EtOAc/ether (1/1)

Sources & evidence

ORD record
ord-01c92dc9ae754fbfa8ce639352e63b35
Source dataset
uspto-grants-2011_01
Patent number
US07863314B2

Linked notes

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