2-Aminopyrimidine → 2-Methyl-3-[4-(trifluoromethyl)phenyl]imidazo[1,2-a]pyrimidine

HRID 241432

Reaction equation

HRID 241432 reaction equation
Br[CH:2]([CH3:15])[C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]([F:14])([F:13])[F:12])=[CH:7][CH:6]=1)=O.[NH2:16][C:17]1[N:22]=[CH:21][CH:20]=[CH:19][N:18]=1.C(=O)(O)[O-].[Na+]>CC(O)C>[CH3:15][C:2]1[N:16]=[C:17]2[N:22]=[CH:21][CH:20]=[CH:19][N:18]2[C:3]=1[C:5]1[CH:10]=[CH:9][C:8]([C:11]([F:14])([F:13])[F:12])=[CH:7][CH:6]=1

Participants

5

Reactant 3

HCID 79782-AminopyrimidineHCID 516892Sodium BicarbonateHCID 104238192-Bromo-1-(4-(trifluoromethyl)phenyl)propan-1-one

Product 1

HCID 710597752-Methyl-3-[4-(trifluoromethyl)phenyl]imidazo[1,2-a]pyrimidine

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

In a thermally controlled reactor, stir a mixture of 2-bromo-1-[4-(trifluoromethyl)phenyl]propan-1-one (500 g, 1.78 mol, 1 equiv), IPA (5 L), 2-aminopyrimidine (205 g, 2.13 mol, 1.2 equiv), and sodium bicarbonate (298.8 g, 3.55 mol, 2 equiv) at 80° C. for 18 hours. Cool the suspension, and concentrate in vacuo. Dilute the resulting mixture in DCM (5 L), and wash with brine (2 L). Re-extract the brine wash with DCM (2.5 L); combine all the organic phases; and dry over MgSO4; filter; and collect the filtrate. Concentrate the filtrate to dryness under reduced pressure, and slurry the resulting red gum in Et2O (1.5 L). Collect the resulting solid by filtrate, and air dry for 45 min to give the title compound as a fine, off white solid (108 g, 22% yield). MS (m/z) 278 (M+1).

Workup

  1. temperatureCool the suspension
  2. concentrationconcentrate in vacuo
  3. additionDilute the resulting mixture in DCM (5 L)
  4. washwash with brine (2 L)
  5. washRe-extract the brine wash with DCM (2.5 L)
  6. dry with materialand dry over MgSO4
  7. filtrationfilter
  8. customand collect the filtrate
  9. concentrationConcentrate the filtrate to dryness under reduced pressure
  10. customCollect the resulting solid by filtrate, and air
  11. customdry for 45 min

Sources & evidence

ORD record
ord-705882bb16214e3b947072f0284455fb
Source dataset
uspto-grants-2014_02
Patent number
US08648200B2

Linked notes

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