Water → HCID 86718390, compound

HRID 588071Notes

Reaction equation

HRID 588071 reaction equation
[F:1][C:2]([F:31])([F:30])[CH2:3][O:4][C:5]1[CH:10]=[C:9]([O:11][CH2:12][C:13]([F:16])([F:15])[F:14])[N:8]=[C:7]([NH:17][C:18](=[O:29])[NH:19][C:20]2[S:21][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:23][CH:24]=2)[N:6]=1.[H-].[Na+].[CH3:34][O:35][CH2:36]Br.O>CN(C)C=O>[CH3:34][O:35][CH2:36][N:17]([C:7]1[N:6]=[C:5]([O:4][CH2:3][C:2]([F:1])([F:30])[F:31])[CH:10]=[C:9]([O:11][CH2:12][C:13]([F:16])([F:15])[F:14])[N:8]=1)[C:18](=[O:29])[NH:19][C:20]1[S:21][C:22]([C:25]([F:26])([F:27])[F:28])=[CH:23][CH:24]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 83093Bromomethyl methyl etherHCID 86718391HCID 86718391, compound

Product 1

HCID 86718390HCID 86718390, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 3-(4,6-bis(2,2,2-trifluoroethoxy)pyrimidin-2-yl)-1-(5-(trifluoromethyl)thiophen-2-yl)urea (1) (150 mg, 0.31 mmol) in anhydrous dimethyl formamide (DMF, 1.5 mL) at ambient temperature was added NaH (6.6 mg, 0.28 mmol, 60% dispersion in mineral oil). After stirring 20 minutes a solution of bromomethyl methyl ether (35 mg, 0.28 mmol) in anhydrous DMF (0.5 mL) was added. After 2.5 h the reaction was judged complete by TLC analysis. To the reaction was carefully added H2O (2 mL). The reaction was extracted with EtOAc (10 mL). The EtOAc solution was washed with H2O (3×7 mL) followed by brine (7 mL). The organics were dried (Na2SO4), filtered and evaporated to give crude product. The crude material was purified by silica gel chromatography (0 to 8% EtOAc in pet ether) to afford 3-(methoxymethyl)-3-(4,6-bis(2,2,2-trifluoroethoxy)pyrimidin-2-yl)-1-(5-(trifluoromethyl)thiophen-2-yl)urea (4) as an off white solid (18 mg, 11%), mp 118-119° C.; 1H NMR (400 MHz, Acetone-d6) δ 11.84 (s, 1H), 7.41-7.28 (m, 1H), 6.66 (dd, J=4.1, 0.9 Hz, 1H), 6.18 (s, 1H), 5.54 (s, 2H), 5.02 (q, J=8.6 Hz, 4H), 3.27 (s, 3H); ESIMS m/z 527 ([M−H]+).

Workup

  1. additionwas added
  2. extractionThe reaction was extracted with EtOAc (10 mL)
  3. washThe EtOAc solution was washed with H2O (3×7 mL)
  4. dry with materialThe organics were dried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated
  7. customto give crude product
  8. customThe crude material was purified by silica gel chromatography (0 to 8% EtOAc in pet ether)

Sources & evidence

ORD record
ord-1482e1e57fbb4c3990b9db352355c90f
Source dataset
uspto-grants-2016_01
Patent number
US09227957B2

Reaction notes

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