Potassium Carbonate → HCID 24994332, compound

HRID 423510Notes

Reaction equation

HRID 423510 reaction equation
Cl.Cl.[CH3:3][S:4]([C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:14]=[CH:15][C:16]([O:19][CH2:20][CH:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)=[N:17][CH:18]=2)=[CH:9][CH:8]=1)(=[O:6])=[O:5].Cl[C:28]1[N:33]=[CH:32][C:31]([CH2:34][CH3:35])=[CH:30][N:29]=1.C([O-])([O-])=O.[K+].[K+]>CC#N>[CH2:34]([C:31]1[CH:30]=[N:29][C:28]([N:24]2[CH2:25][CH2:26][CH:21]([CH2:20][O:19][C:16]3[CH:15]=[CH:14][C:13]([C:10]4[CH:11]=[CH:12][C:7]([S:4]([CH3:3])(=[O:5])=[O:6])=[CH:8][CH:9]=4)=[CH:18][N:17]=3)[CH2:22][CH2:23]2)=[N:33][CH:32]=1)[CH3:35]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 35727632-Chloro-5-ethylpyrimidineHCID 66673101HCID 66673101, compound

Product 1

HCID 24994332HCID 24994332, compoundYield 66.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 5-[4-(methylsulfonyl)phenyl]-2-[(4-piperidinylmethyl)oxy]pyridine dihydrochloride (Example 71, Step 1, 0.16 g, 0.38 mmol), 2-chloro-5-ethylpyrimidine (0.1 mL, 0.76 mmol) and K2CO3 (0.26 g, 1.91 mmol) in CH3CN (3 mL) was degassed, purged with N2 and heated at 80° C. overnight. After more CH3CN (2 mL) was added, the reaction mixture was heated at 80° C. for two days. The mixture was allowed to cool to ambient temperature, water was added and the mixture was extracted with EtOAc. The combined organic extract was washed with brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product as a light yellow solid. The crude product was purified by chromatography on a silica gel column eluted with 2:5 EtOAc/CH2Cl2 to give 0.114 g (66%) of the title compound as a white solid. 1H NMR (400 MHz, CDCl3): δ 8.39 (d, 1H, J=2.5 Hz), 8.20 (bs, 2H), 8.01 (d, 2H, J=8.3 Hz), 7.82 (dd, 1H, Ja=8.7 Hz, Jb=2.6 Hz), 7.70 (d, 2H, J=8.3 Hz), 6.85 (d, 1H, J=8.5 Hz), 4.81 (bs, 2H), 4.24 (d, 2H, J=6.3 Hz), 3.08 (s, 3H), 3.05-2.85 (m, 2H), 2.55-2.40 (m, 2H), 2.20-2.05 (m, 1H), 2.00-1.90 (m, 2H), 1.45-1.30 (m, 2H), 1.19 (t, 3H, J=7.5 Hz); LRMS (ESI), m/z 453 (M+H).

Workup

  1. customwas degassed
  2. custompurged with N2
  3. additionAfter more CH3CN (2 mL) was added
  4. temperaturethe reaction mixture was heated at 80° C. for two days
  5. temperatureto cool to ambient temperature
  6. additionwater was added
  7. extractionthe mixture was extracted with EtOAc
  8. extractionThe combined organic extract
  9. washwas washed with brine
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationthe filtrate was concentrated
  13. customto give the crude product as a light yellow solid
  14. customThe crude product was purified by chromatography on a silica gel column
  15. washeluted with 2:5 EtOAc/CH2Cl2

Sources & evidence

ORD record
ord-046d441c0cd344d2bba4872bfbb88cb4
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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