Methylamine → 3-Cyclopropyl-1-(2-fluoro-4-iodophenyl)-6-(methylamino)-2,4(1H,3H)-pyrimidinedione

HRID 75651Notes

Reaction equation

HRID 75651 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]([CH:17]2[CH2:19][CH2:18]2)[C:4](=[O:20])[CH:3]=1.[CH3:21][NH2:22]>CO>[CH:17]1([N:5]2[C:4](=[O:20])[CH:3]=[C:2]([NH:22][CH3:21])[N:7]([C:8]3[CH:13]=[CH:12][C:11]([I:14])=[CH:10][C:9]=3[F:15])[C:6]2=[O:16])[CH2:19][CH2:18]1

Participants

4

Reactant 2

HCID 6329MethylamineHCID 597171116-chloro-3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-1H-pyrimidine-2,4-dione2×

Product 1

HCID 597171713-Cyclopropyl-1-(2-fluoro-4-iodophenyl)-6-(methylamino)-2,4(1H,3H)-pyrimidinedione

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To a 1:2 mixture (62.9 g) of 6-chloro-3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-1H-pyrimidine-2,4-dione 50 and 6-chloro-1-cyclopropyl-3-(2-fluoro-4-iodophenyl)-1H-pyrimidine-2,4-dione 51 obtained in Step 3 were added methanol (189 ml) and a solution (126 ml) of 40% methylamine in methanol, and the mixture was stirred at room temperature for 2 hrs. The precipitated crystals were filtered off and the filtrate was concentrated under reduced pressure. The residue was extracted with chloroform (200 ml) and water (200 ml), and the organic layer was washed with brine (200 ml) and dried over anhydrous magnesium sulfate. Anhydrous magnesium sulfate was filtered off and the filtrate was concentrated under reduced pressure to give a 2:1 mixture (34.55 g) of 3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-6-methylamino-1H-pyrimidine-2,4-dione 52 and 1-cyclopropyl-3-(2-fluoro-4-iodophenyl)-6-methylamino-1H-pyrimidine-2,4,-dione 53 as yellow crystals, which were used for the next step without purification.

Workup

  1. filtrationThe precipitated crystals were filtered off
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. extractionThe residue was extracted with chloroform (200 ml) and water (200 ml)
  4. washthe organic layer was washed with brine (200 ml)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationAnhydrous magnesium sulfate was filtered off
  7. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-827efd42b179419d9eb264645f3ae510
Source dataset
uspto-grants-2014_09
Patent number
US08835443B2

Reaction notes

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