p-Toluenesulfonic acid → HCID 67256257, compound

HRID 410500Notes

Reaction equation

HRID 410500 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[F:9])[NH2:5].Cl[C:11]1[N:16]=[C:15]([C:17]([F:20])([F:19])[F:18])[CH:14]=[CH:13][N:12]=1.O1CCOCC1.CC1C=CC(S(O)(=O)=O)=CC=1>C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]([NH:5][C:11]2[N:16]=[C:15]([C:17]([F:20])([F:19])[F:18])[CH:14]=[CH:13][N:12]=2)[CH:6]=[CH:7][C:8]=1[F:9]

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 312751,4-DioxaneHCID 27739122-Chloro-4-(trifluoromethyl)pyrimidineHCID 27792863-Bromo-4-fluoroaniline

Product 1

HCID 67256257HCID 67256257, compoundYield 89.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To 3-bromo-4-fluoroaniline (0.76 g, 4.0 mmol) and 2-chloro-4-(trifluoromethyl)pyrimidine (0.73 g, 4.0 mmol) was added dioxane (13.33 mL) and p-TSA (0.761 g, 4.0 mmol). The reaction was sealed and was heated at reflux overnight. The reaction was cooled to room temperature and was diluted with ethyl acetate, washed with saturated aqueous NaHCO3, and the organic was dried over sodium sulfate and filtered before concentration. The crude product was purified by flash chromatography (25:75 ethyl acetate:hexanes) to afford N-(3-bromo-4-fluorophenyl)-4-(trifluoromethyl)pyrimidin-2-amine (1.2 g, 3.57 mmol, 89%) as a pale yellowish solid. 1H NMR (500 MHz, CDCl3): δ 8.68 (d, J=4.9 Hz, 1H); 7.99-7.96 (m, 1H); 7.51 (d, J=8.4 Hz, 1H); 7.29 (s, 1H); 7.14 (t, J=8.5 Hz, 1H); 7.10 (d, J=4.9 Hz, 1H). rhSYK activity=+

Workup

  1. customThe reaction was sealed
  2. temperaturewas heated
  3. temperatureat reflux overnight
  4. washwashed with saturated aqueous NaHCO3
  5. dry with materialthe organic was dried over sodium sulfate
  6. filtrationfiltered before concentration
  7. customThe crude product was purified by flash chromatography (25:75 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-40a6676fa629417283ccdeeafbb461e9
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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