Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1) → HCID 66558121, compound

HRID 2405913Notes

Reaction equation

HRID 2405913 reaction equation
[CH:1]1([C:7]2[CH:8]=[N:9][N:10]([CH2:12][CH2:13][C@@:14]([CH3:29])([S:25]([CH3:28])(=[O:27])=[O:26])[C:15]([NH:17][O:18]C3CCCCO3)=[O:16])[CH:11]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CC1C=CC(S([O-])(=O)=O)=CC=1.C1C=C[NH+]=CC=1>CCO>[CH:1]1([C:7]2[CH:8]=[N:9][N:10]([CH2:12][CH2:13][C@@:14]([CH3:29])([S:25]([CH3:28])(=[O:26])=[O:27])[C:15]([NH:17][OH:18])=[O:16])[CH:11]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 86710230HCID 86710230, compound

Product 1

HCID 66558121HCID 66558121, compoundYield 65.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of (2R)-4-(4-cyclohexyl-1H-pyrazol-1-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (260 mg, 0.608 mmol, 1 eq) in EtOH (6 mL), was added PPTS (45.7 mg, 0.182 mmol, 0.3 eq), and the reaction mixture was heated at reflux overnight. The crude product mixture was purified by reverse phase HPLC (Column: Phenomenex Gemini NX 150×21.2 mm 5μ; Flow rate 28 mL/min; conditions: 5-95% Water/MeOH containing 0.1% NH4OH) to give (2R)-4-(4-cyclohexyl-1H-pyrazol-1-yl)-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide (137 mg, 65% yield). 1H NMR (400 MHz, DMSO-d6) δ 7.48 (s, 1H), 7.25 (s, 1H), 4.13-4.03 (m, 1H), 3.97-3.85 (m, 1H), 3.02 (s, 3H), 2.68-2.57 (m, 1H), 2.43-2.33 (m, 1H), 2.21-2.08 (m, 1H), 1.89-1.80 (m, 1H), 1.74-1.57 (m, 3H), 1.42 (s, 3H), 1.25 (s, 6H). LC-MS M+H+344.1.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux overnight
  3. customThe crude product mixture was purified by reverse phase HPLC (Column: Phenomenex Gemini NX 150×21.2 mm 5μ; Flow rate 28 mL/min; conditions: 5-95% Water/MeOH containing 0.1% NH4OH)

Sources & evidence

ORD record
ord-a9ceb863417142a985b463dd7013d424
Source dataset
uspto-grants-2014_08
Patent number
US08809333B2

Reaction notes

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