Potassium Carbonate → N-pyrimidinyl piperidine sulfonamide

HRID 842246Notes

Reaction equation

HRID 842246 reaction equation
FC(F)(F)C1C=CC(OC2CCN(S(C3(C(OC)=O)CCN([C:23]4[N:28]=[C:27](C(F)(F)F)[CH:26]=[CH:25][N:24]=4)CC3)(=O)=O)CC2)=CC=1.[N:41]1([S:47]([NH2:50])(=[O:49])=[O:48])[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]1.C([O-])=O.[NH4+].C(=O)([O-])[O-].[K+].[K+].ClC1N=C(C(F)(F)F)C=CN=1>CO.CN(C)C=O>[N:24]1[CH:25]=[CH:26][CH:27]=[N:28][C:23]=1[NH:50][S:47]([N:41]1[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]1)(=[O:49])=[O:48]

Participants

8

Reactant 5

HCID 11430Potassium CarbonateHCID 2767411-PiperidinesulfonamideHCID 2723923Ammonium formateHCID 27739122-Chloro-4-(trifluoromethyl)pyrimidineHCID 22052660Methyl 4-[[4-[4-(trifluoromethyl)phenoxy]-1-piperidinyl]-sulfonyl]-1-[4-(trifluoromethyl)-2-pyrimidinyl]-4-piperidinecarboxylate

Product 1

HCID 22052662N-pyrimidinyl piperidine sulfonamideYield 76%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

Part G: Preparation of methyl 4-[[4-[4-(trifluoromethyl)phenoxy]-1-piperidinyl]-sulfonyl]-1-[4-(trifluoromethyl)-2-pyrimidinyl]-4-piperidinecarboxylate. To a slurry of the piperidine sulfonamide from part F (6.3 g, 12.0 mmol) in methanol (25 mL) was added ammonium formate (2.2 g, 34.5 mmol). The system was purged with nitrogen for 10 min. The nitrogen stream was removed and palladium on carbon (1.2 g of 10 weight % on activated carbon, 50% water) was added. The reaction was refluxed for forty five min, cooled, filtered through Celite under N2, and concentrated in vacuo. The residue (4.5 g, 10 mmol) was dissolved in dry dimethylformamide (20 mL) and potassium carbonate (4.14 g, 30 mmol) and 2-chloro-4-trifluoromethylpyrimidine (2.4 mL, 20 mmol) were added. The reaction was stirred at 70° C. for 3 hr, and then concentrated in vacuo, The residue was taken up in ethyl acetate and filtered through Celite. The filtrate washed with water two times, saturated sodium chloride solution, dried over Na2SO4, filtered, and concentrated in vacuo. The product was recrystallized (methanol) to give the N-pyrimidinyl piperidine sulfonamide as a white solid (4.51 g, 76%).

Workup

  1. customThe system was purged with nitrogen for 10 min
  2. customThe nitrogen stream was removed
  3. additionpalladium on carbon (1.2 g of 10 weight % on activated carbon, 50% water) was added
  4. temperatureThe reaction was refluxed for forty five min
  5. temperaturecooled
  6. filtrationfiltered through Celite under N2
  7. concentrationconcentrated in vacuo
  8. concentrationconcentrated in vacuo
  9. filtrationfiltered through Celite
  10. washThe filtrate washed with water two times, saturated sodium chloride solution
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customThe product was recrystallized (methanol)

Sources & evidence

ORD record
ord-4a98f606c7864cf7943e8daff44f382f
Source dataset
uspto-grants-2002_04
Patent number
US06372758B1

Reaction notes

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