Methyl iodide → 3-Methyl-3-(4,6-bis(2,2,2-trifluoroethoxy)pyrimidin-2-yl)-1-methyl-1-(5-(trifluoromethyl)thiophen-2-yl)urea

HRID 588070Notes

Reaction equation

HRID 588070 reaction equation
[H-].[Na+].[F:3][C:4]([F:34])([F:33])[CH2:5][O:6][C:7]1[CH:12]=[C:11]([O:13][CH2:14][C:15]([F:18])([F:17])[F:16])[N:10]=[C:9]([NH:19][C:20](=[O:32])[N:21]([CH3:31])[C:22]2[S:23][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:25][CH:26]=2)[N:8]=1.[CH3:35]I>C1COCC1>[CH3:35][N:19]([C:9]1[N:8]=[C:7]([O:6][CH2:5][C:4]([F:3])([F:33])[F:34])[CH:12]=[C:11]([O:13][CH2:14][C:15]([F:18])([F:17])[F:16])[N:10]=1)[C:20](=[O:32])[N:21]([CH3:31])[C:22]1[S:23][C:24]([C:27]([F:28])([F:29])[F:30])=[CH:25][CH:26]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 73775810HCID 73775810, compound

Product 1

HCID 867183893-Methyl-3-(4,6-bis(2,2,2-trifluoroethoxy)pyrimidin-2-yl)-1-methyl-1-(5-(trifluoromethyl)thiophen-2-yl)urea

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of NaH (18 mg, 0.36 mmol) in anhydrous THF (3 mL) was added a solution of the 3-(4,6-bis(2,2,2-trifluoroethoxy)pyrimidin-2-yl)-1-methyl-1-(5-(trifluoromethyl)thiophen-2-yl)urea (2) (150 mg, 0.30 mmol). The reaction was stirred for 10 minutes after which time gas evolution had subsided. To the reaction was added methyl iodide (51.2 mg, 0.36 mmol). The reaction was stirred at ambient temperature for 2 h. The reaction was quenched with H2O (5 mL) and extracted with t-butyl ethyl ether (3×5 mL). The organics were combined and extracted with an equal amount of H2O. The organics were dried (MgSO4), filtered and concentrated to afford crude product. The crude material was purified by silica gel chromatography (5% EtOAc in pet ether) to afford 3-methyl-3-(4,6-bis(2,2,2-trifluoroethoxy)pyrimidin-2-yl)-1-methyl-1-(5-(trifluoromethyl)thiophen-2-yl)urea (6) as an off white solid (31 mg, 20%), mp 113-114° C.; 1H NMR (400 MHz, Acetone-d6) δ 7.35-7.24 (m, 1H), 6.73 (d, J=4.2 Hz, 1H), 5.88 (s, 1H), 4.76 (q, J=8.7 Hz, 4H), 3.35 (s, 3H), 3.28 (s, 3H); ESIMS m/z 513 ([M+H]+).

Workup

  1. stirringThe reaction was stirred at ambient temperature for 2 h
  2. customThe reaction was quenched with H2O (5 mL)
  3. extractionextracted with t-butyl ethyl ether (3×5 mL)
  4. extractionextracted with an equal amount of H2O
  5. dry with materialThe organics were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto afford crude product
  9. customThe crude material was purified by silica gel chromatography (5% EtOAc in pet ether)

Sources & evidence

ORD record
ord-12b641cfb5ca45098b8e4224b41f1d18
Source dataset
uspto-grants-2016_01
Patent number
US09227957B2

Reaction notes

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