Potassium Carbonate → HCID 57929852, compound

HRID 1930006Notes

Reaction equation

HRID 1930006 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:13]([C:14]2[CH:15]=[CH:16][C:17]3[N:18]([C:20]([CH:23]([CH3:25])[CH3:24])=[N:21][N:22]=3)[N:19]=2)=[CH:12][N:11]([CH:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)[N:10]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:39][CH2:40][O:41][CH3:42]>CN(C=O)C>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:13]([C:14]2[CH:15]=[CH:16][C:17]3[N:18]([C:20]([CH:23]([CH3:24])[CH3:25])=[N:21][N:22]=3)[N:19]=2)=[CH:12][N:11]([CH:26]2[CH2:31][CH2:30][N:29]([CH2:39][CH2:40][O:41][CH3:42])[CH2:28][CH2:27]2)[N:10]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 809722-Bromoethyl methyl ether3×HCID 57929875HCID 57929875, compound

Product 1

HCID 57929852HCID 57929852, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

The 6-(3-(2,4-difluorophenyl)-1-(piperidin-4-yl)-1H-pyrazol-4-yl)-3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazine (0.15 g, 0.35 mmol; Example #Q.1.2) was dissolved in DMF (4 mL) and then the K2CO3 (0.10 g, 0.71 mmol) and 1-bromo-2-methoxyethane (0.075 g, 0.53 mmol) were added. The mixture was heated at about 65° C. in an oil bath for about 1 h then another portion of 1-bromo-2-methoxyethane (0.075 g, 0.53 mmol) was added. After about 1 h, a third portion of 1-bromo-2-methoxyethane (0.075 g, 0.53 mmol) was added. The mixture was heated for about 1 h longer then cooled and concentrated under reduced pressure. The material was purified by RP-HPLC (Table 1, Method d). The appropriate fractions were concentrated and then basified with 2N NaOH and then extracted with EtOAc. Drying over MgSO4 and evaporating gave an oil which was purified further by flash chromatography on silica with DCM/MeOH (9:1) as an eluent. Concentration of the appropriate fractions followed by trituration with Et2O/heptane resulted in a solid which was collected by filtration to provide the title compound (0.086 g, 50%): LC/MS (Table 1, Method a) Rt=1.90 min; MS m/z: 482.2 (M+H)+.

Workup

  1. temperatureThe mixture was heated for about 1 h longer
  2. temperaturecooled
  3. concentrationconcentrated under reduced pressure
  4. customThe material was purified by RP-HPLC (Table 1, Method d)
  5. concentrationThe appropriate fractions were concentrated
  6. extractionextracted with EtOAc
  7. dry with materialDrying over MgSO4
  8. customevaporating
  9. customgave an oil which
  10. customwas purified further by flash chromatography on silica with DCM/MeOH (9:1) as an eluent
  11. customresulted in a solid which
  12. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-128e44b64b93475d83a363f561612cd4
Source dataset
uspto-grants-2012_05
Patent number
US08188083B2

Reaction notes

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