Acetic Acid → HCID 86729883, compound

HRID 922530Notes

Reaction equation

HRID 922530 reaction equation
[ClH:1].[NH2:2][C@@H:3]1[CH2:5][C@H:4]1[C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13]([C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[CH:17][CH:16]=2)=[O:14])=[CH:8][CH:7]=1.[C:27](O)(=O)[CH3:28].[CH:31]1([CH:34]=O)[CH2:33][CH2:32]1.CN(C=O)C.[C:41](OCC)(=O)[CH3:42]>CO.O>[ClH:1].[CH:27]1([CH2:28][N:2]([CH2:34][CH:31]2[CH2:32][CH2:33]2)[C@@H:3]2[CH2:5][C@H:4]2[C:6]2[CH:7]=[CH:8][C:9]([NH:12][C:13]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)=[CH:17][CH:16]=3)=[O:14])=[CH:10][CH:11]=2)[CH2:42][CH2:41]1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 6228DimethylformamideHCID 8857Ethyl AcetateHCID 123114Cyclopropanecarboxaldehyde3×HCID 86729866HCID 86729866, compound

Product 1

HCID 86729883HCID 86729883, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of N-[4-(trans-2-aminocyclopropyl)phenyl]biphenyl-4-carboxamide hydrochloride (100 mg) in methanol (5.4 mL) were added acetic acid (0.6 mL), cyclopropanecarbaldehyde (0.023 mL) and 2-picoline-borane complex (44 mg). The mixture was stirred at room temperature for 21 hr, and DMF (4 mL) and 2-picoline-borane complex (29.3 mg) were added. The mixture was stirred at room temperature for 2 hr, and cyclopropanecarbaldehyde (0.010 mL) was added. The mixture was stirred at room temperature for 3 hr, and cyclopropanecarbaldehyde (0.008 mL) was added. The mixture was stirred at room temperature for 1 hr, water and ethyl acetate were added, and the mixture was concentrated under reduced pressure. To the residue was added saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted twice with ethyl acetate. The extracts were combined, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate), and 10% hydrochloric acid methanol solution (1.0 mL) was added to the obtained product. The solvent was evaporated under reduced pressure to give the title compound (26.1 mg).

Workup

  1. stirringThe mixture was stirred at room temperature for 2 hr
  2. stirringThe mixture was stirred at room temperature for 3 hr
  3. stirringThe mixture was stirred at room temperature for 1 hr
  4. concentrationthe mixture was concentrated under reduced pressure
  5. additionTo the residue was added saturated aqueous sodium hydrogen carbonate solution
  6. extractionthe mixture was extracted twice with ethyl acetate
  7. washwashed with saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customThe solvent was evaporated under reduced pressure
  10. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate), and 10% hydrochloric acid methanol solution (1.0 mL)
  11. additionwas added to the obtained product
  12. customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-bede93fbbc584dddb59c0bfc6a6e21c5
Source dataset
uspto-grants-2016_03
Patent number
US09278931B2

Reaction notes

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