Trifluoroacetic acid → HCID 69093386, compound

HRID 2409104Notes

Reaction equation

HRID 2409104 reaction equation
[NH2:1][C:2]1[C:3]([CH3:13])=[N:4][N:5]([C:7]([CH3:12])([CH3:11])[C:8]([NH2:10])=[O:9])[CH:6]=1.Cl[C:15]1[N:20]=[C:19]([NH:21][CH3:22])[C:18]([C:23]([F:26])([F:25])[F:24])=[CH:17][N:16]=1.FC(F)(F)C(O)=O.C([O-])([O-])=O.[Na+].[Na+]>COCCO.O>[CH3:12][C:7]([N:5]1[CH:6]=[C:2]([NH:1][C:15]2[N:20]=[C:19]([NH:21][CH3:22])[C:18]([C:23]([F:26])([F:24])[F:25])=[CH:17][N:16]=2)[C:3]([CH3:13])=[N:4]1)([CH3:11])[C:8]([NH2:10])=[O:9]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 210775872-Chloro-N-methyl-5-(trifluoromethyl)pyrimidin-4-amineHCID 69082882HCID 69082882, compound

Product 1

HCID 69093386HCID 69093386, compoundYield 51.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80192-MethoxyethanolSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 2-(4-amino-3-methyl-1H-pyrazol-1-yl)-2-methylpropanamide (250 mg, 1.37 mmol) in 2-methoxyethanol (5 mL) was added 2-chloro-N-methyl-5-(trifluoromethyl)pyrimidin-4-amine (290 mg, 1.37 mmol) and trifluoroaceticacid (156 mg, 1.37 mmol), the reaction was stirred at 70° C. for about 0.5 h. The reaction mixture was cooled to ambient temperature followed with the addition of water (10 mL) and the pH of solution was adjusted to 8 with sat. Na2CO3 The aqueous phase was extracted with ethyl acetate (10 mL×3), the combined organic phase was dried over anhydrous sodium sulfate, filtered and concentrated to dry to give a residue which was purified by column chromatography on silica gel (CH2Cl2:MeOH=20:1) to give 2-methyl-2-(3-methyl-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-1H-pyrazol-1-yl)propanamide (250 mg, 51%) as white solid. LCMS (m/z) ES+358 (m+H).

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. extractionwas extracted with ethyl acetate (10 mL×3)
  3. dry with materialthe combined organic phase was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto dry
  7. customto give a residue which
  8. customwas purified by column chromatography on silica gel (CH2Cl2:MeOH=20:1)

Sources & evidence

ORD record
ord-4f665e35d3004581beca09f9631afffe
Source dataset
uspto-grants-2014_08
Patent number
US08815882B2

Reaction notes

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