2-Amino-4-(trifluoromethyl)pyridine → 6-bromo-4-methyl-N-[4-(trifluoromethyl)pyridine-2-yl]pyridine-2-amine

HRID 2283482Notes

Reaction equation

HRID 2283482 reaction equation
Br[C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([Br:9])[N:3]=1.[NH2:10][C:11]1[CH:16]=[C:15]([C:17]([F:20])([F:19])[F:18])[CH:14]=[CH:13][N:12]=1.CC(C)([O-])C.[Na+]>>[Br:9][C:4]1[N:3]=[C:2]([NH:10][C:11]2[CH:16]=[C:15]([C:17]([F:19])([F:18])[F:20])[CH:14]=[CH:13][N:12]=2)[CH:7]=[C:6]([CH3:8])[CH:5]=1

Participants

4

Reactant 3

HCID 27783152-Amino-4-(trifluoromethyl)pyridineHCID 112881742,6-DIBROMO-4-METHYLPYRIDINEHCID 23676156Sodium t-butoxide

Product 1

HCID 866807956-bromo-4-methyl-N-[4-(trifluoromethyl)pyridine-2-yl]pyridine-2-amine

Conditions

Temperature
25 °C

Procedure

To a flask containing 2,6-dibromo-4-methylpyridine (13.9 g, 55.5 mmol) and 2-amino-4-trifluoromethylpyridine (9.0 g, 55.5 mmol) was added nitrogen sparged dioxane (180 mL). Sodium tert-butoxide (5.87 g, 61.1 mmol) and 1,1′-bis(di-tert-butylphsophino)ferrocene palladium dichloride (0.905 g, 1.4 mmol) were then added, and the slurry was evacuated and refilled with nitrogen. The mixture was stirred at 25° C. for 15 minutes and then heated to 75° C. for 12 hours. The reaction was cooled to 25° C., water (20 mL) was added, and the mixture was extracted with ethyl actetate (2×200 mL). The combined extracts were dried over Na2SO4, filtered, concentrated in vacuo. The residue was purified via chromatography on silica gel to afford 6-bromo-4-methyl-N-[4-(trifluoromethyl)pyridine-2-yl]pyridine-2-amine as a white solid. MS ESI calcd. for C12H10BrF3N3 [M+H]+ 332 and 334. found 332 and 334. 1H NMR (600 MHz, DMSO-d6) δ 10.40 (s, 1H), 8.46 (d, J=6.0 Hz, 1H), 7.90 (s, 1H), 7.60 (s, 1H), 7.18 (d, J=6.0 Hz, 1H), 7.00 (s, 1H), 2.25 (s, 3H).

Workup

  1. additionwas added nitrogen
  2. customsparged dioxane (180 mL)
  3. customthe slurry was evacuated
  4. additionrefilled with nitrogen
  5. temperatureheated to 75° C. for 12 hours
  6. temperatureThe reaction was cooled to 25° C.
  7. additionwater (20 mL) was added
  8. extractionthe mixture was extracted with ethyl actetate (2×200 mL)
  9. dry with materialThe combined extracts were dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified via chromatography on silica gel

Sources & evidence

ORD record
ord-5d05730aa28342379146c1f1e6fdd9a7
Source dataset
uspto-grants-2015_09
Patent number
US09145391B2

Reaction notes

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