Diisopropylethylamine → HCID 86710240, compound

HRID 2405928Notes

Reaction equation

HRID 2405928 reaction equation
[CH3:1][C@@:2]([S:19]([CH3:22])(=[O:21])=[O:20])([CH2:6][CH2:7][N:8]1[CH:12]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:10]=[N:9]1)[C:3]([OH:5])=O.CCN(C(C)C)C(C)C.[O:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH:33]1[O:38][NH2:39].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O.O>[CH3:1][C@@:2]([S:19]([CH3:22])(=[O:21])=[O:20])([CH2:6][CH2:7][N:8]1[CH:12]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:10]=[N:9]1)[C:3]([NH:39][O:38][CH:33]1[CH2:34][CH2:35][CH2:36][CH2:37][O:32]1)=[O:5]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 70817707HCID 70817707, compound

Product 1

HCID 86710240HCID 86710240, compoundYield 61.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (2R)-2-methyl-2-(methylsulfonyl)-4-(4-phenyl-1H-pyrazol-1-yl)butanoic acid (0.855 g, 2.65 mmol, 1 eq) in DMF (20 mL) was added DIPEA (1.06 g, 7.96 mmol, 1.45 mL, 3.eq), O-tetrahydro-2H-pyran-2-yl-hydroxylamine (0.621 g, 5.30 mmol, 2 eq) and HATU (1.54 g, 3.98 mmol, 1.5 eq). The reaction was allowed to stir at RT overnight. The mixture was diluted with EtOAc and water. The aqueous layer was extracted several times with EtOAc, dried (MgSO4), filtered and concentrated. The crude product mixture was purified by flash chromatography on a 40 g silica column eluting with 0-100% EtOAc/DCM to give (2R)-2-methyl-2-(methylsulfonyl)-4-(4-phenyl-1H-pyrazol-1-yl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (685 mg, 61% yield). LC-MS M−H 420.3.

Workup

  1. extractionThe aqueous layer was extracted several times with EtOAc
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product mixture was purified by flash chromatography on a 40 g silica column
  6. washeluting with 0-100% EtOAc/DCM

Sources & evidence

ORD record
ord-04e3eb1bb86b402a9ce7fcf03112f6ba
Source dataset
uspto-grants-2014_08
Patent number
US08809333B2

Reaction notes

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