Sodium Carbonate → 4,4,4-trifluoro-N-{[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}but-2-en-1-amine

HRID 1851720Notes

Reaction equation

HRID 1851720 reaction equation
Br[CH2:2][CH:3]=[CH:4][C:5]([F:8])([F:7])[F:6].C(=O)([O-])[O-].[Na+].[Na+].[CH3:15][O:16][CH2:17][C:18]1[S:22][C:21]2=[N:23][C:24]([C:28]([F:31])([F:30])[F:29])=[C:25]([CH2:26][NH2:27])[N:20]2[N:19]=1>CN(C)C=O>[F:6][C:5]([F:8])([F:7])[CH:4]=[CH:3][CH2:2][NH:27][CH2:26][C:25]1[N:20]2[C:21]([S:22][C:18]([CH2:17][O:16][CH3:15])=[N:19]2)=[N:23][C:24]=1[C:28]([F:29])([F:31])[F:30]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 536401074-Bromo-1,1,1-trifluorobut-2-eneHCID 709767161-[2-(Methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methanamine

Product 1

HCID 891570854,4,4-trifluoro-N-{[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}but-2-en-1-amine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-bromo-1,1,1-trifluorobut-2-ene (0.782 g, 4.14 mmol, 1.4 eq) and sodium carbonate (0.376 g, 3.55 mmol, 1.2 eq) are added to suspension of 1-[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methanamine a19 in N,N-dimethylformamide (15 ml). The mixture is stirred overnight at room temperature to afford crude 4,4,4-trifluoro-N-{[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}but-2-en-1-amine a20. Ethoxycarbonyl isocyanate (0.51 g, 4.43 mmol, 1.5 eq) is added to the reaction mixture. After 4 h, the reaction is not complete and ethoxycarbonyl isocyanate (0.5 eq) is added again. The reaction mixture is stirred overnight to afford crude ethyl ({[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}[(4,4,4-trifluorobut-2-en-1-yl]carbamoyl)carbamate a21. Potassium tert-butoxide is added and the reaction mixture is heated at 75° C. for 4 h. After cooling, the reaction mixture is extracted with toluene (2×80 ml). The cumulated organic layers are dried over MgSO4, filtered and condensed under reduced pressure. The residue is purified by chromatography over silicagel (eluent: CH2Cl2/MeOH 99/1) to afford 602 mg of a mixture of ethyl 5-(2,2-difluoroethenyl)-3-{[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-2-oxoimidazolidine-1-carboxylate a22 (as the major compound) and ethyl 3-{[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-2-oxo-5-(2,2,2-trifluoroethyl)imidazolidine-1-carboxylate a23.

Sources & evidence

ORD record
ord-568fc0d6d7ee487aa3d874b297fb1b7c
Source dataset
uspto-grants-2015_02
Patent number
US08957218B2

Reaction notes

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