Sodium Hydroxide → HCID 66778224, compound

HRID 2091408Notes

Reaction equation

HRID 2091408 reaction equation
[C:1]([C:3]1[C:4]([O:9][C:10]2[CH:11]=[CH:12][C:13]3[O:17][C:16]([CH:18]([NH:25][C:26]4[CH:31]=[CH:30][C:29]([C:32]([N:34]([CH3:42])[CH2:35][CH2:36][C:37]([O:39]CC)=[O:38])=[O:33])=[CH:28][CH:27]=4)[CH:19]4[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]4)=[C:15]([CH3:43])[C:14]=3[CH:44]=2)=[N:5][CH:6]=[CH:7][CH:8]=1)#[N:2].[OH-].[Na+]>C(O)C.O1CCCC1>[C:1]([C:3]1[C:4]([O:9][C:10]2[CH:11]=[CH:12][C:13]3[O:17][C:16]([CH:18]([NH:25][C:26]4[CH:27]=[CH:28][C:29]([C:32]([N:34]([CH3:42])[CH2:35][CH2:36][C:37]([OH:39])=[O:38])=[O:33])=[CH:30][CH:31]=4)[CH:19]4[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]4)=[C:15]([CH3:43])[C:14]=3[CH:44]=2)=[N:5][CH:6]=[CH:7][CH:8]=1)#[N:2]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 66777964HCID 66777964, compound

Product 1

HCID 66778224HCID 66778224, compoundYield 33%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Ethyl 3-{[(4-{[{5-[(3-cyanopyridin-2-yl)oxy]-3-methyl-1-benzofuran-2-yl}(cyclohexyl)methyl]amino}phenyl)carbonyl](methyl)amino}-propanoate (234 mg) obtained in Example A197 was dissolved in ethanol (1.5 mL) and tetrahydrofuran (1.5 mL), 1N aqueous sodium hydroxide solution (0.78 mL) was added to the solution, and the mixture was stirred at room temperature for 30 min. The solvent was evaporated under reduced pressure, water (4 mL) was added, and the mixture was neutralized with 1N hydrochloric acid (0.78 mL) under ice-cooling. The resulting precipitate was collected by filtration and dried. The obtained residue was purified by preparative HPLC “instrument: Gilson Inc., preparative HPLC system; column: Develosil ODS-UG-10, S-5 μm, 50×100 mm; solvent: SOLUTION A; 0.1% trifluoroacetic acid-containing water, SOLUTION B; 0.1% trifluoroacetic acid-containing acetonitrile, (SOLUTION A:SOLUTION B=95:5-0:100); flow rate: 150 mL/min; detection method: UV 220 nm”. To the fractionated fraction was added saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated to give the title compound (73 mg, 33%) as a colorless amorphous form.

Workup

  1. customThe solvent was evaporated under reduced pressure, water (4 mL)
  2. additionwas added
  3. temperaturecooling
  4. filtrationThe resulting precipitate was collected by filtration
  5. customdried
  6. customThe obtained residue was purified by preparative HPLC “instrument
  7. addition0.1% trifluoroacetic acid-containing water, SOLUTION B
  8. addition0.1% trifluoroacetic acid-containing acetonitrile, (SOLUTION A:SOLUTION B=95:5-0:100)
  9. additionTo the fractionated fraction was added saturated aqueous sodium hydrogen carbonate solution
  10. extractionthe mixture was extracted with ethyl acetate
  11. washThe organic layer was washed with saturated brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. filtrationAfter filtration
  14. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-8e69da43f0ab47feb9b2c3f1e2cd6960
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

Loading…