Water → 1-{[6-Chloro-2-(methoxymethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-4-(2-fluoroethyl)pyrrolidin-2-one

HRID 69564Notes

Reaction equation

HRID 69564 reaction equation
[F-:1].C([N+](CCCC)(CCCC)CCCC)CCC.CC1C=CC(S(O[CH2:30][CH2:31][CH:32]2[CH2:36][C:35](=[O:37])[N:34]([CH2:38][C:39]3[N:46]4[C:42]([S:43][C:44]([CH2:47][O:48][CH3:49])=[N:45]4)=[N:41][C:40]=3[Cl:50])[CH2:33]2)(=O)=O)=CC=1.O>C1COCC1>[Cl:50][C:40]1[N:41]=[C:42]2[N:46]([C:39]=1[CH2:38][N:34]1[CH2:33][CH:32]([CH2:31][CH2:30][F:1])[CH2:36][C:35]1=[O:37])[N:45]=[C:44]([CH2:47][O:48][CH3:49])[S:43]2

Participants

5

Reactant 3

HCID 962WaterHCID 2724141Tetrabutylammonium FluorideHCID 866714522-(1-{[6-Chloro-2-(methoxymethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-5-oxopyrrolidin-3-yl)ethyl 4-methylbenzenesulfonate

Product 1

HCID 529117951-{[6-Chloro-2-(methoxymethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-4-(2-fluoroethyl)pyrrolidin-2-oneYield 22%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 1M solution of tetrabutylammonium fluoride in THF solution (4 ml) is added to 2-(1-{[6-chloro-2-(methoxymethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-5-oxopyrrolidin-3-yl)ethyl 4-methylbenzenesulfonate a39 (308 mg, 0.617 mmol, 1 eq). The resulting solution is irradiated in a microwave apparatus (Biotage) at 100° C. for 1 h. Water (10 ml) is added to the reaction mixture, and the crude compound is extracted by ethyl acetate (4×10 ml). The cumulated organic layer are washed successively by a saturated NH4Cl aqueous solution (2×10 ml), water (2×10 ml), dried over MgSO4, filtered and condensed under reduced pressure. The residue is purified by flash chromatography over silicagel (eluent: CH2Cl2/MeOH 99:1) to afford 47 mg of pure 1-{[6-chloro-2-(methoxymethyl)-imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-4-(2-fluoroethyl)pyrrolidin-2-one 28.

Workup

  1. customThe resulting solution is irradiated in a microwave apparatus (Biotage) at 100° C. for 1 h
  2. extractionthe crude compound is extracted by ethyl acetate (4×10 ml)
  3. washThe cumulated organic layer are washed successively by a saturated NH4Cl aqueous solution (2×10 ml), water (2×10 ml)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customcondensed under reduced pressure
  7. customThe residue is purified by flash chromatography over silicagel (eluent: CH2Cl2/MeOH 99:1)

Sources & evidence

ORD record
ord-4635be6a7ab242f5b5ce8553b220a7f9
Source dataset
uspto-grants-2014_09
Patent number
US08822508B2

Reaction notes

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