Sodium hydride → 6-(1-Methanesulfonyl-piperidin-4-yloxy)-pyridine-3-sulfonic acid (4-fluoro-phenyl)-isobutyl-amide

HRID 1049018Notes

Reaction equation

HRID 1049018 reaction equation
[CH3:1][S:2]([N:5]1[CH2:10][CH2:9][CH:8]([OH:11])[CH2:7][CH2:6]1)(=[O:4])=[O:3].[H-].[Na+].[F:14][C:15]1[CH:20]=[CH:19][C:18]([N:21]([CH2:32][CH:33]([CH3:35])[CH3:34])[S:22]([C:25]2[C:26](Cl)=[N:27][CH:28]=[CH:29][CH:30]=2)(=[O:24])=[O:23])=[CH:17][CH:16]=1.C([O-])(O)=O.[Na+]>C1COCC1.O>[F:14][C:15]1[CH:16]=[CH:17][C:18]([N:21]([CH2:32][CH:33]([CH3:35])[CH3:34])[S:22]([C:25]2[CH:26]=[N:27][C:28]([O:11][CH:8]3[CH2:7][CH2:6][N:5]([S:2]([CH3:1])(=[O:4])=[O:3])[CH2:10][CH2:9]3)=[CH:29][CH:30]=2)(=[O:24])=[O:23])=[CH:19][CH:20]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 222729811-Methanesulfonylpiperidin-4-olHCID 86721872Chloro-pyridine-3-sulfonic acid (4-fluoro-phenyl)-isobutyl-amide

Product 1

HCID 762841816-(1-Methanesulfonyl-piperidin-4-yloxy)-pyridine-3-sulfonic acid (4-fluoro-phenyl)-isobutyl-amideYield 64.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-methanesulfonyl-piperidin-4-ol (86 mg, 482 μmol) in anhydrous THF (5 mL) at room temperature was added NaH (60% dispersion in mineral oil, 21 mg, 526 μmol) and the reaction was stirred at room temperature for 15 minutes. Chloro-pyridine-3-sulfonic acid (4-fluoro-phenyl)-isobutyl-amide (150 mg, 439 μmol) was added and the reaction stirred at room temperature for 45 minutes then heated at 80° C. for 2 hours. Water and saturated NaHCO3 were added and then extracted with EtOAc, washed with brine, dried with Na2SO4 then concentrated and purified by silica gel column chromatography (0-25% EtOAc in cyclohexane) to give the title compound (137 mg). 1H NMR (400 MHz, DMSO): δ 8.30 (dd, J=2.6, 0.67 Hz, 1H), 7.75 (dd, J=8.8, 2.60 Hz, 1H), 7.19-7.20 (m, 4H), 6.97 (dd, J=8.8, 0.7 Hz, 1H), 5.23-5.25 (m, 1H), 3.39 (d, J=8.8 Hz, 4H), 3.13 (ddd, J=12.2, 8.56, 3.46 Hz, 2H), 2.91 (s, 3H), 2.04-2.09 (m, 2H), 1.78-1.80 (m, 2H), 1.44 (dd, J=13.6, 6.9 Hz, 1H), 0.85 (d, J=6.6 Hz, 6H). LCMS (m/z, Method B) ES+ 485.9 [M+1]+.

Workup

  1. stirringthe reaction stirred at room temperature for 45 minutes
  2. temperaturethen heated at 80° C. for 2 hours
  3. extractionextracted with EtOAc
  4. washwashed with brine
  5. dry with materialdried with Na2SO4
  6. concentrationthen concentrated
  7. custompurified by silica gel column chromatography (0-25% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-73269d8b62a64ae3afbc34289077a860
Source dataset
uspto-grants-2016_07
Patent number
US09382222B2

Reaction notes

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