Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → 2-(4-bromo-3-(trifluoromethyl)phenyl)-N-(5-(pyrazin-2-yl)pyridin-2-yl)acetamide

HRID 592157Notes

Reaction equation

HRID 592157 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=O)=[CH:4][C:3]=1[C:12]([F:15])([F:14])[F:13].[N:16]1[CH:21]=[CH:20][N:19]=[CH:18][C:17]=1[C:22]1[CH:23]=[CH:24][C:25]([NH2:28])=[N:26][CH:27]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(OCC)(=O)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH:28][C:25]2[CH:24]=[CH:23][C:22]([C:17]3[CH:18]=[N:19][CH:20]=[CH:21][N:16]=3)=[CH:27][N:26]=2)=[O:11])=[CH:4][C:3]=1[C:12]([F:15])([F:14])[F:13]

Participants

6

Reactant 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 269863604-Bromo-3-(trifluoromethyl)benzeneacetic acidHCID 592592255-(Pyrazin-2-yl)pyridin-2-amine

Product 1

HCID 682471702-(4-bromo-3-(trifluoromethyl)phenyl)-N-(5-(pyrazin-2-yl)pyridin-2-yl)acetamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 2-(4-bromo-3-(trifluoromethyl)phenyl)acetic acid 46-6 (128 mg, 0.5 mmol), 5-(pyrazin-2-yl)pyridin-2-amine 86-3 (95 mg, 0.55 mmol) and o-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 214 mg, 0.55 mmol) in DMF (2 mL) was added diispropylethyl amine (DIEA, 250 μL, 1.5 mmol) at room temperature. The mixture was stirred at room temperature for 2 hours. The mixture was diluted with ethyl acetate (50 mL), washed with saturated NaHCO3 aqueous solution, water and brine, dried over Na2SO4, and concentrated by rotary evaporation. The crude product was purified by silica gel flash chromatography, eluted with 5% methanol in dichloromethane to give 2-(4-bromo-3-(trifluoromethyl)phenyl)-N-(5-(pyrazin-2-yl)pyridin-2-yl)acetamide 118-1 as pale orange solid. MS m/z 438.2 (M+1)

Workup

  1. washwashed with saturated NaHCO3 aqueous solution, water and brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated by rotary evaporation
  4. customThe crude product was purified by silica gel flash chromatography
  5. washeluted with 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-73f5ac5d13e34be6bbd7e4aab0e78a49
Source dataset
uspto-grants-2016_01
Patent number
US09238646B2

Reaction notes

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