Methylamine → 1-(2-fluoro-4-iodophenyl)-3-methyl-6-methylamino-1H-pyrimidine-2,4-dione

HRID 75667Notes

Reaction equation

HRID 75667 reaction equation
Cl[C:2]1[N:7]([C:8]2[CH:13]=[CH:12][C:11]([I:14])=[CH:10][C:9]=2[F:15])[C:6](=[O:16])[N:5]([CH3:17])[C:4](=[O:18])[CH:3]=1.CN.FC1C=C(I)C=C[C:23]=1[N:29]1C(=O)C=C(NC)N(C)C1=O>CO>[F:15][C:9]1[CH:10]=[C:11]([I:14])[CH:12]=[CH:13][C:8]=1[N:7]1[C:2]([NH:29][CH3:23])=[CH:3][C:4](=[O:18])[N:5]([CH3:17])[C:6]1=[O:16]

Participants

5

Reactant 3

HCID 6329MethylamineHCID 59717010HCID 59717010, compound2×HCID 59717068HCID 59717068, compound

Product 1

HCID 597172291-(2-fluoro-4-iodophenyl)-3-methyl-6-methylamino-1H-pyrimidine-2,4-dioneYield 79.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To a 6:5 mixture (75.7 g) of 6-chloro-1-(2-fluoro-4-iodophenyl)-3-methyl-1H-pyrimidine-2,4-dione 65 and 6-chloro-3-(2-fluoro-4-iodophenyl)-1-methyl-1H-pyrimidine-2,4-dione 66 obtained in Step 3 were added methanol (227 ml) and 40% solution (152 ml) of methylamine in methanol, and the mixture was stirred at room temperature for 2.5 hrs. The reaction mixture was concentrated under reduced pressure, and toluene (150 ml) and water (150 ml) were added to the residue, and the mixture was stirred under heating at reflux for 30 min. After allowing to return to room temperature, the crystals were collected by filtration and dried to give a 6:5 mixture (59.6 g, yield 79.9%) of 1-(2-fluoro-4-iodophenyl)-3-methyl-6-methylamino-1H-pyrimidine-2,4-dione 67 and 3-(2-fluoro-4-iodophenyl)-1-methyl-6-methylamino-1H-pyrimidine-2,4-dione 68 as pale-yellow crystals.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure, and toluene (150 ml) and water (150 ml)
  2. additionwere added to the residue
  3. stirringthe mixture was stirred
  4. temperatureunder heating
  5. temperatureat reflux for 30 min
  6. customto return to room temperature
  7. filtrationthe crystals were collected by filtration
  8. customdried

Sources & evidence

ORD record
ord-c321968c420141a08807124ff88bacf3
Source dataset
uspto-grants-2014_09
Patent number
US08835443B2

Reaction notes

Loading…