Potassium Carbonate → HCID 86646696, compound

HRID 2381129Notes

Reaction equation

HRID 2381129 reaction equation
[F:1][C:2]([F:26])([F:25])[C:3]1[N:7]2[N:8]=[C:9]([N:12]3[CH2:17][CH2:16][CH:15]([C:18]4[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=4)[CH2:14][CH2:13]3)[CH:10]=[CH:11][C:6]2=[N:5][N:4]=1.Br[CH2:28][CH2:29][CH2:30][C:31]([F:34])([F:33])[F:32].C(=O)([O-])[O-].[K+].[K+]>CC(N(C)C)=O>[F:32][C:31]([F:34])([F:33])[CH2:30][CH2:29][CH2:28][O:24][C:21]1[CH:22]=[CH:23][C:18]([CH:15]2[CH2:16][CH2:17][N:12]([C:9]3[CH:10]=[CH:11][C:6]4[N:7]([C:3]([C:2]([F:1])([F:25])[F:26])=[N:4][N:5]=4)[N:8]=3)[CH2:13][CH2:14]2)=[CH:19][CH:20]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 5210064-Bromo-1,1,1-trifluorobutaneHCID 367300784-(1-(3-(Trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl)piperidin-4-yl)phenol

Product 1

HCID 86646696HCID 86646696, compoundYield 37%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
200 °C

Procedure

4-[1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl]phenol (obtained as described in Example 5.2, preparation of starting materials) (200 mg, 0.55 mmol), 4-bromo-1,1,1-trifluorobutane (526 mg, 2.75 mmol) and potassium carbonate (152 mg, 1.10 mmol) were suspended in DMA (4 mL) and sealed into a microwave tube. The reaction was heated to 200° C. for 30 minutes in the microwave reactor and cooled to room temperature. The mixture was evaporated to dryness and redissolved in DCM (20 mL) and the solution was washed with water (20 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% ammonia) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford 6-{4-[4-(4,4,4-trifluorobutoxy)phenyl]piperidin-1-yl}-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine (95 mg, 37%) as a solid.

Workup

  1. customsealed into a microwave tube
  2. temperaturecooled to room temperature
  3. customThe mixture was evaporated to dryness
  4. dissolutionredissolved in DCM (20 mL)
  5. washthe solution was washed with water (20 mL)
  6. dry with materialThe organic layer was dried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customto afford crude product
  10. customThe crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length)
  11. additionFractions containing the desired compound
  12. customwere evaporated to dryness

Sources & evidence

ORD record
ord-b891ed7f49384f30ab88f4189cde5449
Source dataset
uspto-grants-2012_09
Patent number
US08258140B2

Reaction notes

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