Malonic Acid → 1-Cyclopropyl-3-(2-fluoro-4-iodophenyl)pyrimidine-2,4,6-trione

HRID 75649Notes

Reaction equation

[CH:1]1([NH:4][C:5]([NH:7][C:8]2[CH:13]=[CH:12][C:11]([I:14])=[CH:10][C:9]=2[F:15])=[O:6])[CH2:3][CH2:2]1.[C:16](O)(=[O:21])[CH2:17][C:18](O)=[O:19].C(OC(=O)C)(=O)C.C(Cl)(=O)C>O.C1(C)C=CC=CC=1>[CH:1]1([N:4]2[C:18](=[O:19])[CH2:17][C:16](=[O:21])[N:7]([C:8]3[CH:13]=[CH:12][C:11]([I:14])=[CH:10][C:9]=3[F:15])[C:5]2=[O:6])[CH2:2][CH2:3]1

Participants

Conditions

Temperature: 60 °C

Procedure

To 1-cyclopropyl-3-(2-fluoro-4-iodophenyl)urea 48 (61.0 g) obtained in Step 1 and malonic acid 4 (19.9 g) were added acetic anhydride (300 ml) and acetyl chloride (27.2 ml), and the mixture was stirred under a nitrogen atmosphere at 60° C. for 3 hrs. After allowing to cool to room temperature, the reaction mixture was added dropwise to water-toluene [2:1 (volume ratio), 900 ml] with stirring. The precipitated crystals were collected by filtration and dried to give 1-cyclopropyl-3-(2-fluoro-4-iodophenyl)pyrimidine-2,4,6-trione 49 (60.9 g, yield 82%) as pale-yellow crystals.

Workup

temperatureto cool to room temperature
stirringwith stirring
filtrationThe precipitated crystals were collected by filtration
customdried

Sources & evidence

ORD record: ord-98b987ece858456f86306871045cc49e
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08835443B2

Reaction notes

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