Ethanol → HCID 69083753, compound

HRID 1023467Notes

Reaction equation

HRID 1023467 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:12][CH2:11][CH2:10][N:9]2[C:13]2[CH:18]=[CH:17][N:16]=[C:15]([NH2:19])[CH:14]=2)=[CH:4][CH:3]=1.[C:20]([N:28]=C=O)(=[O:27])C1C=CC=CC=1.C(O)C.C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[CH2:12][CH2:11][CH2:10][N:9]2[C:13]2[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]([NH2:28])=[O:27])[CH:14]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 702EthanolHCID 11430Potassium CarbonateHCID 78210Benzoyl isocyanateHCID 69085942HCID 69085942, compound

Product 1

HCID 69083753HCID 69083753, compoundYield 55.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

4-[2-(4-Fluoro-phenyl)-pyrrolidin-1-yl]-pyridin-2-ylamine (61 mg, 0.24 mmol) and benzoyl isocynate (52 mg, 0.36 mmol) are mixed in DCM (2.0 mL). The reaction is sealed and heated at 50° C. for 16 hrs. Then the solvent is removed and to the residue are added ethanol (2.0 mL) and potassium carbonate (49 mg, 0.36 mmol). The mixture is then heated at 80° C. for 45 min. The solvent is removed and the residue is partitioned between water (35 mL) and EtOAc (55 mL). The aqueous layer is separated and extracted with EtOAc (2×30 mL). The organic layers are combined and concentrated to give the crude product. Purification by silica flash column chromatography using MeOH in DCM (gradient from 0% to 10%) followed by re-crystallization from DCM/heptane affords 40 mg of the titled product.

Workup

  1. customThe reaction is sealed
  2. customThen the solvent is removed and to the residue
  3. temperatureThe mixture is then heated at 80° C. for 45 min
  4. customThe solvent is removed
  5. customthe residue is partitioned between water (35 mL) and EtOAc (55 mL)
  6. customThe aqueous layer is separated
  7. extractionextracted with EtOAc (2×30 mL)
  8. concentrationconcentrated
  9. customto give the crude product
  10. customPurification by silica flash column chromatography
  11. customfollowed by re-crystallization from DCM/heptane

Sources & evidence

ORD record
ord-2d718ff333c94ece923fd302c0bf2fa5
Source dataset
uspto-grants-2014_05
Patent number
US08722709B2

Reaction notes

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