Water → HCID 15952855, compound

HRID 1924276Notes

Reaction equation

HRID 1924276 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.[CH3:25][S-:26].[Na+].O.C(OCC)(=O)C>C1COCC1>[CH3:25][S:26][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 8857Ethyl AcetateHCID 4378561Sodium methanethiolateHCID 15952659HCID 15952659, compound

Product 1

HCID 15952855HCID 15952855, compoundYield 26%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 1-{[6-chloro-2-(trifluoromethyl)imidazo[1,2-b]pyridazin-3-yl]methyl}-4-propylpyrrolidin-2-one 30 (400 mg, 1.11 mmol) and sodium methanethiolate (155 mg, 2.22 mmol, 2.2 eq) in THF is heated in a microwave apparatus (300 W, Tmax 150° C.) during 15 minutes. After cooling to room temperature, hydrolysis (15 ml of water), extraction (ethyl acetate, 3×15 ml), the cumulated organic layers are dried over MgSO4, filtered and condensed under reduce pressure to afford an oil which is purified under preparative chromatography over silicagel (Gradient: CH2Cl2 to CH2Cl2/MeOH/NH4OH 99/1/0.1 (v/v/v)). Recrystallization in diisopropyl ether affords 1-{[6-(methylthio)-2-(trifluoromethyl)imidazo[1,2-b]pyridazin-3-yl]methyl}-4-propylpyrrolidin-2-one 46.

Workup

  1. temperatureAfter cooling to room temperature
  2. dry with materialthe cumulated organic layers are dried over MgSO4
  3. filtrationfiltered
  4. customcondensed
  5. customto afford an oil which
  6. customis purified under preparative chromatography over silicagel (Gradient: CH2Cl2 to CH2Cl2/MeOH/NH4OH 99/1/0.1 (v/v/v))
  7. customRecrystallization in diisopropyl ether

Sources & evidence

ORD record
ord-63048089bcda4200990f9eee21278d3b
Source dataset
uspto-grants-2012_05
Patent number
US08178533B2

Reaction notes

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