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

HRID 1404237Notes

Reaction equation

HRID 1404237 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.[CH3:9][C:10]1[C:15]([NH2:16])=[CH:14][CH:13]=[C:12]([C:17]([F:20])([F:19])[F:18])[N:11]=1.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.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([NH:16][C:15]2[C:10]([CH3:9])=[N:11][C:12]([C:17]([F:20])([F:18])[F:19])=[CH:13][CH:14]=2)=[N:3][CH:4]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 693532,5-DibromopyridineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 35218502-methyl-6-(trifluoromethyl)pyridin-3-amine

Product 1

HCID 66615910(5-Bromo-pyridin-2-yl)-(2-methyl-6-trifluoromethyl-pyridin-3-yl)-amine

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

2,5-dibromopyridine (474 mg, 2 mmol) and 2-Methyl-6-trifluoromethyl-pyridin-3-ylamine (352 g, 2 mmol) were dissolved in 1,4-dioxane (4 mL) in a pressure vessel. Pd2dba3 (55 mg, 0.06 mmol) and XANTPHOS (46 mg, 0.08 mmol) were added, followed by cesium carbonate (1.3 g, 4 mmol). The mixture was sparged with nitrogen for 10 minutes, then the vessel was sealed and heated at 100° C. for 18 hours. The mixture was partitioned between EtOAc and saturated aqueous NH4Cl, then the organic layer was washed with brine, dried with magnesium sulfate, filtered, and concentrated via rotary evaporation. The crude material was purified via column chromatography on silica gel, eluting with a gradient of EtOAc/hexanes (7-60%) to obtain the target compound as a solid: 1H NMR (400 MHz, CDCl3) δ ppm 2.62 (s, 3 H) 6.36 (br. s., 1 H) 6.75 (d, J=8.59 Hz, 1 H) 7.53 (d, J=8.34 Hz, 1 H) 7.69 (dd, J=8.84, 2.53 Hz, 1 H) 8.32-8.37 (m, 2 H); MS (M+H)+ 334.7.

Workup

  1. customThe mixture was sparged with nitrogen for 10 minutes
  2. customthe vessel was sealed
  3. customThe mixture was partitioned between EtOAc and saturated aqueous NH4Cl
  4. washthe organic layer was washed with brine
  5. dry with materialdried with magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated via rotary evaporation
  8. customThe crude material was purified via column chromatography on silica gel
  9. washeluting with a gradient of EtOAc/hexanes (7-60%)

Sources & evidence

ORD record
ord-e9ae5b8bf6e44188a4af4efb2123930e
Source dataset
uspto-grants-2014_12
Patent number
US08912208B2

Reaction notes

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