Water → HCID 66571724, compound

HRID 1851722Notes

Reaction equation

HRID 1851722 reaction equation
[Cl:1][C:2]([F:27])([F:26])[CH2:3][CH:4]1[CH2:8][N:7]([CH2:9][C:10]2[N:17]3[C:13]([S:14][C:15]([CH2:18][O:19][CH3:20])=[N:16]3)=[N:12][C:11]=2[C:21]([F:24])([F:23])[F:22])[C:6](=[O:25])[NH:5]1.[OH-].[Na+].I[CH3:31].O>C(Cl)Cl.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[Cl:1][C:2]([F:26])([F:27])[CH2:3][CH:4]1[CH2:8][N:7]([CH2:9][C:10]2[N:17]3[C:13]([S:14][C:15]([CH2:18][O:19][CH3:20])=[N:16]3)=[N:12][C:11]=2[C:21]([F:22])([F:23])[F:24])[C:6](=[O:25])[N:5]1[CH3:31]

Participants

7

Reactant 4

HCID 962WaterHCID 6328Methyl iodide3×HCID 14798Sodium HydroxideHCID 66571720HCID 66571720, compound

Product 1

HCID 66571724HCID 66571724, compoundYield 43%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of (+4-(2-chloro-2,2-difluoroethyl)-1-{[2-(methoxymethyl)-6-(trifluoro-methyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}imidazolidin-2-one 14 (120 mg, 0.277 mmol) in CH2Cl2 (12 ml) is added, at 0° C., sodium hydroxide (3.96 ml, 1M solution), tetrabutylammonium bromide (82 mg, 0.1 eq.) and iodomethane (0.035 ml, 2 eq.). The mixture is stirred at room temperature for 120 h. Iodomethane (0.060 ml) is added and the mixture is stirred at room temperature for 24 h. Iodomethane is added (2×0.060 ml) and the mixture is stirred for 72 h. Water is added and the reaction mixture is extracted with CH2Cl2 (2 times), dried over MgSO4, filtered and condensed under reduced pressure. The residue is purified by chromatography (basic conditions; gradient; eluent: H2O/CH3CN/NH4OH 60/40/0.1 to 30/70/0.1; 10 min) to afford 54 mg of pure (+)-4-(2-chloro-2,2-difluoroethyl)-1-{[2-(methoxymethyl)-6-(trifluoromethyl) imidazo[2,1-b][1,3,4]-thiadiazol-5-yl]methyl}-3-methylimidazolidin-2-one 22.

Workup

  1. stirringthe mixture is stirred at room temperature for 24 h
  2. stirringthe mixture is stirred for 72 h
  3. extractionthe reaction mixture is extracted with CH2Cl2 (2 times)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customcondensed under reduced pressure
  7. customThe residue is purified by chromatography (basic conditions; gradient; eluent: H2O/CH3CN/NH4OH 60/40/0.1 to 30/70/0.1; 10 min)

Sources & evidence

ORD record
ord-947b2705c6f94178bdfc850c06ebe4b2
Source dataset
uspto-grants-2015_02
Patent number
US08957218B2

Reaction notes

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