Water → HCID 178439459, compound

HRID 1896478Notes

Reaction equation

HRID 1896478 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:15][N:16]3[CH2:20][CH:19]([CH2:21][CH2:22][CH3:23])[CH2:18][C:17]3=[O:24])=[C:9]([C:11]([F:14])([F:13])[F:12])[N:10]=2)[N:7]=1.[OH-:25].[Na+].C(#N)C.O>CCCCCC.C(OCC)(=O)C>[OH:25][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:15][N:16]3[CH2:20][CH:19]([CH2:21][CH2:22][CH3:23])[CH2:18][C:17]3=[O:24])=[C:9]([C:11]([F:14])([F:13])[F:12])[N:10]=2)[N:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6342AcetonitrileHCID 14798Sodium HydroxideHCID 15952659HCID 15952659, compound

Product 1

HCID 178439459HCID 178439459, compoundYield 10%

Reagents, catalysts & solvents 1

HCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
150 °C

Procedure

A solution of 1-{[6-chloro-2-(trifluoromethyl)imidazo[1,2-b]pyridazin-3-yl]methyl}-4-propylpyrrolidin-2-one 30 (500 mg, 1.38 mmol), sodium hydroxide (110 mg, 2.77 mmol, 2 eq) in 5 ml of a 1/1 mixture of acetonitrile and water is heated in a microwave oven for 20 min (Tmax 150° C.). Acetonitrile is removed from reaction mixture under reduced pressure, the aqueous layer is acidified using aqueous hydrochloric acid solution and the crude product is then extracted by ethyl acetate (3×20 ml). The cumulated organic layers are dried over MgSO4, filtered and condensed under reduced pressure leading to an oily residue which is purified by preparative chromatography on silicagel (dichloromethane/isopropanol 99/1). The resulting solid is dried in a vacuum oven and recrystallized in ethyl acetate to afford 1-{[6-hydroxy-2-(trifluoromethyl)imidazo[1,2-b]pyridazin-3-yl]methyl}-4-propylpyrrolidin-2-one 45.

Workup

  1. customAcetonitrile is removed from reaction mixture under reduced pressure
  2. extractionthe crude product is then extracted by ethyl acetate (3×20 ml)
  3. dry with materialThe cumulated organic layers are dried over MgSO4
  4. filtrationfiltered
  5. customcondensed under reduced pressure
  6. customis purified by preparative chromatography on silicagel (dichloromethane/isopropanol 99/1)
  7. customThe resulting solid is dried in a vacuum oven
  8. customrecrystallized in ethyl acetate

Sources & evidence

ORD record
ord-1f53a7361af6459eaf82d95514c5296b
Source dataset
uspto-grants-2013_08
Patent number
US08518943B2

Reaction notes

Loading…