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

HRID 1039897Notes

Reaction equation

HRID 1039897 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-df048a4742b74de5b0754b42f0cb59c9
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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