Sodium hydride → HCID 86718392, compound

HRID 588072Notes

Reaction equation

HRID 588072 reaction equation
[CH2:1]([O:8][CH2:9][N:10]([C:23]1[N:28]=[C:27]([O:29][CH2:30][C:31]([F:34])([F:33])[F:32])[CH:26]=[C:25]([O:35][CH2:36][C:37]([F:40])([F:39])[F:38])[N:24]=1)[C:11](=[O:22])[NH:12][C:13]1[S:14][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:16][CH:17]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH3:43][O:44][CH2:45]Br>CN(C=O)C>[CH2:1]([O:8][CH2:9][N:10]([C:23]1[N:28]=[C:27]([O:29][CH2:30][C:31]([F:32])([F:33])[F:34])[CH:26]=[C:25]([O:35][CH2:36][C:37]([F:39])([F:40])[F:38])[N:24]=1)[C:11](=[O:22])[N:12]([CH2:43][O:44][CH3:45])[C:13]1[S:14][C:15]([C:18]([F:19])([F:20])[F:21])=[CH:16][CH:17]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 83093Bromomethyl methyl etherHCID 86718393HCID 86718393, compound

Product 1

HCID 86718392HCID 86718392, compoundYield 69.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 3-(benzyloxymethyl)-3-(4,6-bis(2,2,2-trifluoroethoxy)pyrimidin-2-yl)-1-(5-(trifluoromethyl)thiophen-2-yl)urea (250 mg, 0.41 mmol) in anhydrous DMF (2.5 mL), with an internal temperature of ≦−10° C., was slowly added NaH (20 mg, 0.5 mmol, 60% dispersion in mineral oil). The mixture was stirred 30 minutes resulting in a clear yellow solution. To this solution was slowly added a solution of bromomethyl methyl ether (51.6 mg, 0.41 mmol) in anhydrous DMF (0.5 mL). After 2.5 h the reaction was quenched with ice and diluted with EtOAc (25 mL). The mixture was extracted with H2O (3×15 mL) and brine (15 mL). The EtOAc solution was dried (Na2SO4), filtered and evaporated to give crude product. The crude product was purified by silica gel chromatography (2 to 6% EtOAc in pet ether) to afford the product as a pale yellow gum (185 mg, 69%). 1H NMR (400 MHz, Acetone-d6) δ 7.29-7.08 (m, 6H), 6.82 (d, J=3.9 Hz, 1H), 5.90 (s, 1H), 5.40 (s, 2H), 5.10 (s, 2H), 4.79 (q, J=8.7 Hz, 4H), 4.69 (s, 2H), 3.27 (s, 3H); ESIMS m/z 649 ([M+H]+).

Workup

  1. customwith an internal temperature of ≦−10° C.
  2. customresulting in a clear yellow solution
  3. customAfter 2.5 h the reaction was quenched with ice
  4. additiondiluted with EtOAc (25 mL)
  5. extractionThe mixture was extracted with H2O (3×15 mL) and brine (15 mL)
  6. dry with materialThe EtOAc solution was dried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated
  9. customto give crude product
  10. customThe crude product was purified by silica gel chromatography (2 to 6% EtOAc in pet ether)

Sources & evidence

ORD record
ord-242035d8cfff4924a455555bcf2b101b
Source dataset
uspto-grants-2016_01
Patent number
US09227957B2

Reaction notes

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