Hydrochloric Acid → HCID 86710243, compound

HRID 2405934Notes

Reaction equation

HRID 2405934 reaction equation
[CH3:1][C@@:2]([S:21]([CH3:24])(=[O:23])=[O:22])([CH2:8][CH2:9][N:10]1[CH:14]=[C:13]([C:15]2[CH:20]=[N:19][CH:18]=[CH:17][N:16]=2)[CH:12]=[N:11]1)[C:3]([O:5]CC)=O.[OH-].[Li+].Cl.CN1CCOCC1.[O:35]1[CH2:40][CH2:39][CH2:38][CH2:37][CH:36]1[O:41][NH2:42]>C1COCC1.O.O>[CH3:1][C@@:2]([S:21]([CH3:24])(=[O:22])=[O:23])([CH2:8][CH2:9][N:10]1[CH:14]=[C:13]([C:15]2[CH:20]=[N:19][CH:18]=[CH:17][N:16]=2)[CH:12]=[N:11]1)[C:3]([NH:42][O:41][CH:36]1[CH2:37][CH2:38][CH2:39][CH2:40][O:35]1)=[O:5]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 79724-MethylmorpholineHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 86710242HCID 86710242, compound

Product 1

HCID 86710243HCID 86710243, compoundYield 47.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21881883Oxolane--water (1/1)Solvent

Procedure

To a solution of ethyl (2R)-2-methyl-2-(methylsulfonyl)-4-[4-(pyrazin-2-yl)-1H-pyrazol-1-yl]butanoate (0.32 g, 0.908 mmol) in THF-H2O (20 mL:10 mL) was added lithium hydroxide (0.217 g, 9.08 mmol, 10 eq). The mixture was allowed to stir at room temperature overnight. The mixture was then acidified with 1M HCl and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated to dryness. The solid was taken up in 2-methyltetrahydrofuran (20 mL). N-methyl morpholine (0.185 g, 1.81 mmol, 1.4 eq) was added, followed by CDMT (0.273 g, 1.55 mmol, 1.2 eq). The reaction mixture was allowed to stir for one hour. O-Tetrahydro-2H-pyran-2-yl-hydroxylamine (0.182 g, 1.55 mmol, 1.2 eq) was added, and the reaction mixture was allowed to stir for an additional two hours. Water (20 mL) was added, and the solution was extracted with 2-MeTHF (100 mL). The aqueous layer was re-extracted with 2-MeTHF (150 mL) and the combined organic layers were washed with brine. The organic layer was dried over sodium sulfate, filtered, and concentrated. The crude was purified by flash chromatography, eluting with 0-10% MeOH/EtOAC to give (2R)-2-methyl-2-(methylsulfonyl)-4-[4-(pyrazin-2-yl)-1H-pyrazol-1-yl]-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (182 mg, 33% yield). LC-MS M−H 424.1.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. stirringto stir for one hour
  7. stirringto stir for an additional two hours
  8. extractionthe solution was extracted with 2-MeTHF (100 mL)
  9. extractionThe aqueous layer was re-extracted with 2-MeTHF (150 mL)
  10. washthe combined organic layers were washed with brine
  11. dry with materialThe organic layer was dried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe crude was purified by flash chromatography
  15. washeluting with 0-10% MeOH/EtOAC

Sources & evidence

ORD record
ord-02ce7b8f536444b98b8222d611a7665f
Source dataset
uspto-grants-2014_08
Patent number
US08809333B2

Reaction notes

Loading…