Water → HCID 59177758, compound

HRID 423607Notes

Reaction equation

HRID 423607 reaction equation
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]=[CH:13][C:14]([OH:17])=[N:15][CH:16]=2)=[CH:7][CH:6]=1)(=[O:4])=[O:3].CS(O[CH2:23][CH:24]1[CH2:29][CH2:28][N:27]([C:30]2[O:34][N:33]=[C:32]([CH:35]([CH3:37])[CH3:36])[N:31]=2)[CH2:26][CH2:25]1)(=O)=O.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[CH3:37][CH:35]([C:32]1[N:31]=[C:30]([N:27]2[CH2:26][CH2:25][CH:24]([CH2:23][O:17][C:14]3[CH:13]=[N:12][C:11]([C:8]4[CH:7]=[CH:6][C:5]([S:2]([CH3:1])(=[O:3])=[O:4])=[CH:10][CH:9]=4)=[CH:16][N:15]=3)[CH2:29][CH2:28]2)[O:34][N:33]=1)[CH3:36]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 57930198(1-(3-Isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yl)methyl methanesulfonateHCID 178504683HCID 178504683, compound

Product 1

HCID 59177758HCID 59177758, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 5-[4-(methylsulfonyl)phenyl]-2-pyrazinol (and tautomers thereof) (0.15 g, 0.60 mmol), {1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl methanesulfonate (prepared as in Example 100, Step 4, except that on small scale no heptane wash was performed, 0.25 g, 0.81 mmol) and K2CO3 (0.17 g, 1.20 mmol) in DMF (6 mL) was stirred at ambient temperature overnight, then heated at 100° C. for 5 h. The mixture was cooled to ambient temperature, water was added, and the mixture was extracted with EtOAc (60 mL×2). The combined organic extracts were washed with water, brine and dried over Na2SO4, filtered, and the filtrate was concentrated to a brown solid. The crude material was purified by chromatography on a silica gel column eluted with 1:20 acetone/CH2Cl2 to 1:15 acetone/CH2Cl2 to give 0.14 g (51%) of the title compound as a white solid. 1H NMR (400 MHz, CDCl3): δ 8.55 (d, 1H, J=0.9 Hz), 8.31 (s, 1H), 8.11 (d, 2H, J=8.6 Hz), 8.02 (d, 2H, J=8.6 Hz), 4.30-4.20 (m, 4H), 3.10-3.05 (m, 5H), 2.91 (septet, 1H, J=7.0 Hz), 2.10-2.00 (m, 1H), 2.00-1.90 (m, 2H), 1.55-1.40 (m, 2H), 1.27 (d, 6H, J=6.6 Hz); LRMS (ESI), m/z 458 (M+H).

Workup

  1. washexcept that on small scale no heptane wash
  2. temperatureThe mixture was cooled to ambient temperature
  3. extractionthe mixture was extracted with EtOAc (60 mL×2)
  4. washThe combined organic extracts were washed with water, brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated to a brown solid
  8. customThe crude material was purified by chromatography on a silica gel column
  9. washeluted with 1:20 acetone/CH2Cl2 to 1:15 acetone/CH2Cl2

Sources & evidence

ORD record
ord-27fd375c26b2450aa72067046ef1186c
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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