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

반응식

HRID 75652 반응식
[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

참가 물질

4

반응물 3

HCID 487Methylmalonic AcidHCID 7918Acetic AnhydrideHCID 597171713-Cyclopropyl-1-(2-fluoro-4-iodophenyl)-6-(methylamino)-2,4(1H,3H)-pyrimidinedione2회

생성물 1

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

반응 조건

온도
100 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-0d4d8a4d50154f3cac171ae725b6192c
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08835443B2

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