Methylmalonic Acid → 3-Cyclopropyl-1-(2-fluoro-4-iodophenyl)-5-hydroxy-6,8-dimethylpyrido(2,3-d)pyrimidine-2,4,7(1H,3H,8H)-trione

HRID 75652

Reaction equation

HRID 75652 reaction equation
[CH:1]1([N:4]2[C:9](=[O:10])[CH:8]=[C:7]([NH:11][CH3:12])[N:6]([C:13]3[CH:18]=[CH:17][C:16]([I:19])=[CH:15][C:14]=3[F:20])[C:5]2=[O:21])[CH2:3][CH2:2]1.[CH3:22][CH:23]([C:27]([OH:29])=O)[C:24]([OH:26])=O.C(OC(=O)C)(=O)C>>[CH:1]1([N:4]2[C:9](=[O:10])[C:8]3[C:27]([OH:29])=[C:23]([CH3:22])[C:24](=[O:26])[N:11]([CH3:12])[C:7]=3[N:6]([C:13]3[CH:18]=[CH:17][C:16]([I:19])=[CH:15][C:14]=3[F:20])[C:5]2=[O:21])[CH2:2][CH2:3]1

Participants

4

Reactant 3

HCID 487Methylmalonic AcidHCID 7918Acetic AnhydrideHCID 597171713-Cyclopropyl-1-(2-fluoro-4-iodophenyl)-6-(methylamino)-2,4(1H,3H)-pyrimidinedione2×

Product 1

HCID 597170043-Cyclopropyl-1-(2-fluoro-4-iodophenyl)-5-hydroxy-6,8-dimethylpyrido(2,3-d)pyrimidine-2,4,7(1H,3H,8H)-trioneYield 36.2%

Conditions

Temperature
100 °C

Procedure

To a 2:1 mixture (34.6 g) of 3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-6-methylamino-1H-pyrimidine-2,4-dione 52 and 1-cyclopropyl-3-(2-fluoro-4-iodo-phenyl)6-methylamino-1H-pyrimidine-2,4,-dione 53 obtained in Step 4, and 2-methylmalonic acid 54 (10.2 g) was added acetic anhydride (173 ml), and the mixture was stirred at 100° C. for 2 hrs. After allowing to cool to room temperature, the reaction mixture was concentrated under reduced pressure. Acetone (104 ml) was added to the residue, and the mixture was stirred with heating under reflux for 30 min. After allowing to cool to room temperature, the precipitated crystals were collected by filtration and dried to give 3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-5-hydroxy-6,8-dimethyl-1H,8H-pyrido[2,3-d]pyrimidine-2,4,7-trione 55 (15.1 g, yield from 48, 21%) as colorless crystals.

Workup

  1. temperatureto cool to room temperature
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. additionAcetone (104 ml) was added to the residue
  4. stirringthe mixture was stirred
  5. temperaturewith heating
  6. temperatureunder reflux for 30 min
  7. temperatureto cool to room temperature
  8. filtrationthe precipitated crystals were collected by filtration
  9. customdried

Sources & evidence

ORD record
ord-0d4d8a4d50154f3cac171ae725b6192c
Source dataset
uspto-grants-2014_09
Patent number
US08835443B2

Linked notes

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