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

HRID 2272649Notes

Reaction equation

HRID 2272649 reaction equation
CC(C)([O-])C.[Na+].Br[C:8]1[CH:13]=[C:12]([CH3:14])[CH:11]=[C:10]([Br:15])[N:9]=1.[NH2:16][C:17]1[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[CH:19][N:18]=1>[Pd](Cl)Cl.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2]>[Br:15][C:10]1[N:9]=[C:8]([NH:16][C:17]2[CH:22]=[C:21]([C:23]([F:25])([F:24])[F:26])[CH:20]=[CH:19][N:18]=2)[CH:13]=[C:12]([CH3:14])[CH:11]=1

Participants

5

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

Reagents, catalysts & solvents 1

HCID 178454861HCID 178454861, compoundCatalyst

Conditions

Temperature
25 °C

Procedure

Sodium tert-butoxide (5.87 g, 61.1 mmol) and 1,1′-bis(di-tert-butylphosphino)ferrocene palladium dichloride (0.905 g, 1.4 mmol) were added to a solution of 2,6-dibromo-4-methyl pyridine (13.9 g, 55.5 mmol) and 2-amino-4-trifluoromethyl pyridine (9.0 g, 55.5 mmol) in nitrogen sparged dioxane (180 mL). 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 mixture was cooled to 25° C., water (20 mL) was added, and the mixture was extracted with ethyl acetate (2×200 mL). The combined extracts were dried over sodium sulfate, filtered, concentrated under reduced pressure. The residue was purified by column 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 calc'd. 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. customsparged dioxane (180 mL)
  2. customThe slurry was evacuated
  3. additionrefilled with nitrogen
  4. temperatureheated to 75° C. for 12 hours
  5. temperatureThe reaction mixture was cooled to 25° C.
  6. additionwater (20 mL) was added
  7. extractionthe mixture was extracted with ethyl acetate (2×200 mL)
  8. dry with materialThe combined extracts were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-0f1e0b06de424760a6550ec94c55f744
Source dataset
uspto-grants-2015_09
Patent number
US09120785B2

Reaction notes

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