Trimethylamine → HCID 136236446, compound

HRID 2281918Notes

Reaction equation

HRID 2281918 reaction equation
F[C:2](F)([O:12]C)[CH:3]([C:8]([F:11])(F)F)[C:4]([F:7])([F:6])[F:5].CN(C)C.[F:19][C:20]1[CH:39]=[CH:38][CH:37]=[CH:36][C:21]=1[CH2:22][N:23]1[C:27]([C:28]2[CH:32]=[CH:31][O:30][N:29]=2)=[CH:26][C:25]([C:33](=[NH:35])[NH2:34])=[N:24]1>CN(C=O)C.C(OCC)(=O)C.CO>[F:11][C:8]1[N:34]=[C:33]([C:25]2[CH:26]=[C:27]([C:28]3[CH:32]=[CH:31][O:30][N:29]=3)[N:23]([CH2:22][C:21]3[CH:36]=[CH:37][CH:38]=[CH:39][C:20]=3[F:19])[N:24]=2)[NH:35][C:2](=[O:12])[C:3]=1[C:4]([F:5])([F:6])[F:7]

Participants

7

Reactant 3

HCID 1146TrimethylamineHCID 454591,1,1,3,3-Pentafluoro-3-methoxy-2-(trifluoromethyl)propaneHCID 66633698HCID 66633698, compound2×

Product 1

HCID 136236446HCID 136236446, compoundYield 24%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a cold solution of 2-(difluoro(methoxy)methyl)-1,1,1,3,3,3-hexafluoropropane (81 mg, 1 equiv.) in DMF (876 μl) at 0° C., was added, slowly, trimethylamine (98 μl, 2 equiv.). The mixture was stirred at 0° C. for 1 h. To this mixture, was added a solution of 1-(2-fluorobenzyl)-5-(isoxazol-3-yl)-1H-pyrazole-3-carboximidamide (Intermediate 8C, 100 mg, 1 equiv.) in DMF (876 μl). The mixture was stirred at room temperature for 1 h and heated to 70° C. for an additional 1 h. The mixture was cooled to room temperature. It was diluted in ethyl acetate (100 ml) and washed with water (50 ml×3). The organic layer was dried, filtered and evaporated to give solid. The resulting solid was dissolved in methanol and absorbed onto silica gel. Purification by column chromatography (0 to 100% ethyl acetate in hexanes) gave 6-fluoro-2-(1-(2-fluorobenzyl)-5-(isoxazol-3-yl)-1H-pyrazol-3-yl)-5-(trifluoromethyl)pyrimidin-4(3H)-one (35 mg, 24% yield) as a yellow solid.

Workup

  1. stirringThe mixture was stirred at room temperature for 1 h
  2. temperatureheated to 70° C. for an additional 1 h
  3. temperatureThe mixture was cooled to room temperature
  4. washwashed with water (50 ml×3)
  5. customThe organic layer was dried
  6. filtrationfiltered
  7. customevaporated
  8. customto give solid
  9. customabsorbed onto silica gel
  10. customPurification by column chromatography (0 to 100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-07ce3014eb6845c28d984ef999644413
Source dataset
uspto-grants-2015_09
Patent number
US09139564B2

Reaction notes

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