Acetic Acid → N-(3-bromo-5-methylphenyl)-4-(difluoromethyl)pyrimidin-2-amine

HRID 410407Notes

Reaction equation

HRID 410407 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH:8]([F:10])[F:9])[CH:5]=[CH:4][N:3]=1.[Br:11][C:12]1[CH:13]=[C:14]([CH:16]=[C:17]([CH3:19])[CH:18]=1)[NH2:15].CC(O)=O>O1CCOCC1.C(Cl)Cl>[Br:11][C:12]1[CH:13]=[C:14]([NH:15][C:2]2[N:7]=[C:6]([CH:8]([F:10])[F:9])[CH:5]=[CH:4][N:3]=2)[CH:16]=[C:17]([CH3:19])[CH:18]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 30185263-Bromo-5-methylanilineHCID 717429242-Chloro-4-(difluoromethyl)pyrimidine

Product 1

HCID 67249363N-(3-bromo-5-methylphenyl)-4-(difluoromethyl)pyrimidin-2-amineYield 72.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

The product of Step 1 (4.75 g, 23 mmol) and 3-bromo-5-methylaniline (5.59 g, 30 mmol) were diluted with dioxane (33 mL) to which AcOH (1.32 mL, 23 mmol) was added. The resulting mixture was heated to reflux and kept stirring for 30 h after which it was recooled to room temperature, diluted with CH2Cl2 and absorbed on silica prior to purification by flash chromatography to afford N-(3-bromo-5-methylphenyl)-4-(difluoromethyl)pyrimidin-2-amine (5.2 g, 16.6 mmol). 1H NMR (600 MHz, CDCl3) δ 8.58 (d, J=4.9, 1H), 7.75 (s, 1H), 7.32 (s, 1H), 7.21 (s, 1H), 7.06-6.92 (m, 2H), 6.50-6.27 (m, 1H), 2.30 (s, 3H).

Workup

  1. additionwas added
  2. temperatureThe resulting mixture was heated
  3. temperatureto reflux
  4. customwas recooled to room temperature
  5. customabsorbed on silica
  6. customto purification by flash chromatography

Sources & evidence

ORD record
ord-52b2c69a4d41400a9d697cf06bd5a81d
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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