Dimethylformamide → 5,5-Dimethyl-1-(2-((4-(3-(trifluoromethyl)-2-thienyl)-2-pyrimidinyl)amino)ethyl)-2,4-imidazolidinedione

HRID 2267405Notes

Reaction equation

HRID 2267405 reaction equation
I[C:2]1[CH:6]=[CH:5][S:4][C:3]=1[C:7]1[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH2:14][CH2:15][N:16]2[C:20]([CH3:22])([CH3:21])[C:19](=[O:23])[NH:18][C:17]2=[O:24])[N:8]=1.[F-].[K+].C([Si](CC)(CC)[C:30]([F:33])([F:32])[F:31])C.CN(C=O)C>ClCCl.[Cu]I.CN1C(=O)CCC1>[CH3:21][C:20]1([CH3:22])[N:16]([CH2:15][CH2:14][NH:13][C:9]2[N:8]=[C:7]([C:3]3[S:4][CH:5]=[CH:6][C:2]=3[C:30]([F:33])([F:32])[F:31])[CH:12]=[CH:11][N:10]=2)[C:17](=[O:24])[NH:18][C:19]1=[O:23]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 522689Potassium FluorideHCID 4204914Triethyl(trifluoromethyl)silaneHCID 602045261-(2-(4-(3-Iodothiophen-2-yl)pyrimidin-2-ylamino)ethyl)-5,5-dimethylimidazolidine-2,4-dione

Product 1

HCID 602045345,5-Dimethyl-1-(2-((4-(3-(trifluoromethyl)-2-thienyl)-2-pyrimidinyl)amino)ethyl)-2,4-imidazolidinedione

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
80 °C

Procedure

A sealed tube charged with 1-(2-(4-(3-iodothiophen-2-yl)pyrimidin-2-ylamino)ethyl)-5,5-dimethylimidazolidine-2,4-dione (0.300 g, 0.656 mmol), copper (I) iodide (0.275 g, 1.44 mmol), spray-dried potassium fluoride (0.075 g, 1.3 mmol), triethyl(trifluoromethyl)silane (0.25 mL, 1.3 mmol), DMF (1.0 mL), and NMP (1.0 mL) was heated to 80° C. and allowed to stir for 72 h. At that time, the mixture was diluted with 20 mL dichloromethane and filtered. The pale green filtrate was then purified through Celite and the plug was washed with 10% MeOH/dichloromethane and H2O. The organic solvents were removed from the biphasic mixture in vacuo and the aqueous residue was then partitioned between dichloromethane and H2O. The organic phase was separated, concentrated and the residue purified by flash chromatography, eluting with 1-6% MeOH/dichloromethane to afford the product as a white solid. MS (M+H)+ 400.

Workup

  1. filtrationfiltered
  2. customThe pale green filtrate was then purified through Celite
  3. washthe plug was washed with 10% MeOH/dichloromethane and H2O
  4. customThe organic solvents were removed from the biphasic mixture in vacuo
  5. customthe aqueous residue was then partitioned between dichloromethane and H2O
  6. customThe organic phase was separated
  7. concentrationconcentrated
  8. customthe residue purified by flash chromatography
  9. washeluting with 1-6% MeOH/dichloromethane

Sources & evidence

ORD record
ord-aa32db32b3794369a7161de1e2037c9a
Source dataset
uspto-grants-2010_12
Patent number
US07858785B2

Reaction notes

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