Triethylamine → 2-methyl-2-(methylsulfonyl)-4-[4-(1H-pyrazol-1-yl)phenyl]-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

HRID 533553Notes

Reaction equation

HRID 533553 reaction equation
[CH3:1][C:2]([S:19]([CH3:22])(=[O:21])=[O:20])([CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([N:14]2[CH:18]=[CH:17][CH:16]=[N:15]2)=[CH:10][CH:9]=1)[C:3]([OH:5])=O.O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.[O:41]1[CH2:46][CH2:45][CH2:44][CH2:43][CH:42]1[O:47][NH2:48]>C(Cl)Cl.O>[CH3:1][C:2]([S:19]([CH3:22])(=[O:21])=[O:20])([CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([N:14]2[CH:18]=[CH:17][CH:16]=[N:15]2)=[CH:10][CH:9]=1)[C:3]([NH:48][O:47][CH:42]1[CH2:43][CH2:44][CH2:45][CH2:46][O:41]1)=[O:5]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 665779152-methyl-2-(methylsulfonyl)-4-[4-(1H-pyrazol-1-yl)phenyl]butanoic acid

Product 1

HCID 866687732-methyl-2-(methylsulfonyl)-4-[4-(1H-pyrazol-1-yl)phenyl]-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-Methyl-2-(methylsulfonyl)-4-[4-(1H-pyrazol-1-yl)phenyl]butanoic acid (286 mg, 0.887 mmol) in methylene chloride (8.87 mL) at ambient temperature was added 1,(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (240 mg, 1.2 mmol), 1-hydroxy benzotriazole monohydrate (240 mg, 1.6 mmol), triethyl amine (220 uL, 1.6 mmol) and O-tetrahydro-2H-pyran-2-yl-hydroxylamine (150 mg, 1.3 mmol). The resulting mixture was stirred at ambient temperature overnight. The mixture was diluted with methylene chloride and water. The phases were separated and the aqueous layer was extracted with methylene chloride two times. The organic extracts were combined and dried over magnesium sulfate, filtered and concentrated in vacuo to a crude residue. The crude residue was purified via silica gel chromatography eluting with methylene chloride and methanol. The fractions containing desired product were combined and concentrated in vacuo to afford 2-methyl-2-(methylsulfonyl)-4-[4-(1H-pyrazol-1-yl)phenyl]-N-(tetrahydro-2H-pyran-2-yloxy)butanamide as a solid. 302.9 mg. LCMS: (M−1) 420.3.

Workup

  1. customThe phases were separated
  2. extractionthe aqueous layer was extracted with methylene chloride two times
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo to a crude residue
  6. customThe crude residue was purified via silica gel chromatography
  7. washeluting with methylene chloride and methanol
  8. additionThe fractions containing desired product
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-15f60fdb264f4a81ae59b068e829e791
Source dataset
uspto-grants-2014_10
Patent number
US08853258B2

Reaction notes

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