Water → HCID 24995588, compound

HRID 423638Notes

Reaction equation

HRID 423638 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[C@@H:23]([CH:25]1[CH2:30][CH2:29][N:28]([C:31]2[O:35][N:34]=[C:33]([CH:36]([CH3:38])[CH3:37])[N:32]=2)[CH2:27][CH2:26]1)[CH3:24])(=O)=O.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[CH3:38][CH:36]([C:33]1[N:32]=[C:31]([N:28]2[CH2:27][CH2:26][CH:25]([C@@H: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)[CH3:24])[CH2:30][CH2:29]2)[O:35][N:34]=1)[CH3:37]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 86638749(1R)-1-{1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}ethyl methanesulfonateHCID 178504683HCID 178504683, compound

Product 1

HCID 24995588HCID 24995588, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 5-[4-(methylsulfonyl)phenyl]-2-pyrazinol (and tautomers thereof) (prepared as in Example 145, Step 2, 1.3 g, 5.19 mmol), (1R)-1-{1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}ethyl methanesulfonate (2.23 g, 7.0 mmol, 70% ee) and K2CO3 (1.45 g, 10.4 mmol) in DMF (35 mL) was stirred at 100° C. in a preheated oil bath overnight. The mixture was cooled to ambient temperature, treated with water, and the mixture was extracted with EtOAc (75 mL×2). The combined organic extracts were washed with water, brine and dried over Na2SO4, filtered, and the filtrate was concentrated to a brown oil, which was by chromatography on a silica gel column eluted with 50% EtOAc/hexanes followed by chromatography on an ISCO silica gel column using 0 to 60% EtOAc/hexanes to give 2-[((1S)-1-{1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}ethyl)oxy]-5-[4-(methylsulfonyl)phenyl]pyrazine (0.73 g, 70% ee, 30%) as a white solid. The solid was subjected to chiral separation (similar to conditions used above for Example 158) to yield 0.30 g of the title compound as a white solid. 1H NMR (400 MHz, CDCl3): δ 8.53 (d, 1H, J=1.3 Hz), 8.25 (d, 1H, J=1.3 Hz), 8.10 (d, 2H, J=8.3 Hz), 8.02 (d, 2H, J=8.5 Hz), 5.20-5.10 (m, 1H), 4.35-4.20 (m, 2H), 3.15-3.00 (m, 5H), 2.90 (septet, 1H, J=7.0 Hz), 2.00-1.80 (m, 3H), 1.60-1.40 (m, 2H), 1.34 (d, 3H, J=6.3 Hz), 1.28 (d, 6H, J=6.9 Hz); LRMS (ESI), m/z 472 (M+H).

Workup

  1. temperatureThe mixture was cooled to ambient temperature
  2. extractionthe mixture was extracted with EtOAc (75 mL×2)
  3. washThe combined organic extracts were washed with water, brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated to a brown oil, which
  7. washeluted with 50% EtOAc/hexanes

Sources & evidence

ORD record
ord-0d60e311e4e642a1ac86d06d5e18fa18
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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