Methanesulfonic Acid → N-(3-bromo-5-methylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine

HRID 595146

Reaction equation

HRID 595146 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][N:3]=1.CS(O)(=O)=O.[Br:17][C:18]1[CH:19]=[C:20]([CH:22]=[C:23]([CH3:25])[CH:24]=1)[NH2:21]>O1CCOCC1>[Br:17][C:18]1[CH:19]=[C:20]([NH:21][C:2]2[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][N:3]=2)[CH:22]=[C:23]([CH3:25])[CH:24]=1

Participants

5

Reactant 3

HCID 6395Methanesulfonic AcidHCID 27739122-Chloro-4-(trifluoromethyl)pyrimidineHCID 30185263-Bromo-5-methylaniline

Product 1

HCID 58456396N-(3-bromo-5-methylphenyl)-4-(trifluoromethyl)pyrimidin-2-amineYield 69%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

2-Chloro-4-(trifluoromethyl)pyrimidine (182 g, 995 mmol) and methanesulfonic acid (97.5 g, 1.02 mol) were added sequentially to a solution of 3-bromo-5-methylaniline (162.5 g, 874 mmol) in 1,4-dioxane (2 L). The resulting solution was heated to reflux overnight then cooled and concentrated under reduced pressure. The residue was diluted with water (2 L), adjusted to pH 7-8 with aqueous sodium bicarbonate solution and extracted with EtOAc (2×2 L). The organic layers were combined, washed with water (2×2 L), dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford N-(3-bromo-5-methylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine (200 g, 602 mmol, 69%) as a light yellow solid. MS ESI calcd. For C11H8BrF3N4 [M+H]+ 332, 334.0. found 332, 334. 1H NMR (400 MHz, CDCl3): δ 8.68 (d, J=4.9 Hz, 1H), 7.79 (s, 1H), 7.30 (s, 2H), 7.10-7.06 (m, 2H), 2.36 (s, 3H). Synthetic Reference: PCT Int. Appl., 2011075517; PCT Int. Appl., 2011075515.

Workup

  1. temperatureThe resulting solution was heated
  2. temperatureto reflux overnight
  3. temperaturethen cooled
  4. concentrationconcentrated under reduced pressure
  5. additionThe residue was diluted with water (2 L)
  6. extractionextracted with EtOAc (2×2 L)
  7. washwashed with water (2×2 L)
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-e843d2c567624aedb60a8bd4f0473fe2
Source dataset
uspto-grants-2016_01
Patent number
US09242984B2

Linked notes

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