Cesium carbonate → 5-(3-Fluoropyridin-4-yl)-6-pyridin-3-yl-N-(2,2,2-trifluoro-1-methylethyl)pyrazin-2-amine

HRID 1710731Notes

Reaction equation

HRID 1710731 reaction equation
Cl[C:2]1[N:3]=[C:4]([C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)[C:5]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[F:14])=[N:6][CH:7]=1.Cl.[F:22][C:23]([F:28])([F:27])[CH:24]([NH2:26])[CH3:25].C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[F:14][C:9]1[CH:10]=[N:11][CH:12]=[CH:13][C:8]=1[C:5]1[N:6]=[CH:7][C:2]([NH:26][CH:24]([CH3:25])[C:23]([F:28])([F:27])[F:22])=[N:3][C:4]=1[C:15]1[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 18364314(RS)-2-Amino-1,1,1-trifluoropropane hydrochlorideHCID 594576235-Chloro-2-(3-fluoropyridin-4-yl)-3-pyridin-3-ylpyrazine

Product 1

HCID 594575565-(3-Fluoropyridin-4-yl)-6-pyridin-3-yl-N-(2,2,2-trifluoro-1-methylethyl)pyrazin-2-amineYield 17%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Procedure

An oven dried resealable Schlenk tube was charged with 5-chloro-2-(3-fluoropyridin-4-yl)-3-pyridin-3-ylpyrazine (Preparation 30, 0.100 g, 0.35 mmol), 1,1,1-trifluoropropan-2-amine hydrochloride (0.063 g, 0.42 mmol), caesium carbonate (0.273 g, 0.84 mmol), BINAP (0.0065 g, 0.01 mmol) and toluene (2 mL). The Schlenk tube was subjected to several cycles of evacuation-backfilling with argon, and palladium(II) acetate (0.0015 g, 0.007 mmol) was added. After three new cycles of evacuation-backfilling with argon, the Schlenk tube was capped and placed in an oil bath at 100° C. After stirring overnight, the mixture was cooled and partitioned between ethyl acetate and water. The organic layer was dried (MgSO4) and evaporated and the residue was purified by silica gel chromatography (CH2Cl2/MeOH 95:5) to give the title compound (0.021 g, 17%) as an off-white solid.

Workup

  1. customAn oven dried resealable Schlenk tube
  2. additionwas added
  3. customAfter three new cycles of evacuation-backfilling with argon, the Schlenk tube was capped
  4. customplaced in an oil bath at 100° C
  5. temperaturethe mixture was cooled
  6. custompartitioned between ethyl acetate and water
  7. dry with materialThe organic layer was dried (MgSO4)
  8. customevaporated
  9. customthe residue was purified by silica gel chromatography (CH2Cl2/MeOH 95:5)

Sources & evidence

ORD record
ord-b586ad51c16240838a3cf3babbc4173a
Source dataset
uspto-grants-2010_09
Patent number
US07790728B2

Reaction notes

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