Cesium carbonate → (5-Bromopyrazin-2-yl)-(6-trifluoromethyl-pyridin-3-yl)-amine

HRID 1506797Notes

Reaction equation

HRID 1506797 reaction equation
CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.Br[C:44]1[CH:49]=[N:48][C:47]([Br:50])=[CH:46][N:45]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[F:57][C:58]([F:67])([F:66])[C:59]1[N:64]=[CH:63][C:62]([NH2:65])=[CH:61][CH:60]=1>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[Br:50][C:47]1[N:48]=[CH:49][C:44]([NH:65][C:62]2[CH:63]=[N:64][C:59]([C:58]([F:67])([F:57])[F:66])=[CH:60][CH:61]=2)=[N:45][CH:46]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27377445-Amino-2-(trifluoromethyl)pyridineHCID 114704212,5-dibromopyrazine

Product 1

HCID 86634697(5-Bromopyrazin-2-yl)-(6-trifluoromethyl-pyridin-3-yl)-amineYield 36.3%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

Pd(OAc)2 (0.097 g, 0.432 mmol) and Xantphos (0.25 g, 0.432 mmol) were added to a solution of 2,5-dibromopyrazine (2.05 g, 8.64 mmol) in 15 mL of toluene under argon atmosphere, followed by cesium carbonate (8.44 g, 25.9 mmol) and 6-(trifluoromethyl)pyridin-3-amine (1.4 g, 8.64 mmol). The mixture was degassed for 10 min. The reaction mixture was stirred at 100° C. for 4 h, allowed to warm to room temperature, and diluted with ethyl acetate and water. The separated organic layer was dried over sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified by flash chromatography using 20% ethyl acetate in hexane to afford the title compound (1 g, 36%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 10.34 (s, 1H), 8.88 (d, J=2.5 Hz, 1H), 8.47-8.35 (m, 2H), 8.17 (d, J=1.4 Hz, 1H), 7.84 (d, J=8.7 Hz, 1H). ESI-MS m/z: 319 (M+H)+.

Workup

  1. customThe mixture was degassed for 10 min
  2. temperatureto warm to room temperature
  3. additiondiluted with ethyl acetate and water
  4. dry with materialThe separated organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-0dd0a0073310427d952b6f91be37917c
Source dataset
uspto-grants-2015_12
Patent number
US09221766B2

Reaction notes

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