Methylmalonic Acid → 1-(2-fluoro-4-iodophenyl)-5-hydroxy-3,6,8-trimethyl-1H,8H-pyrido[2,3-d]pyrimidine-2,4,7-trione

HRID 75668

反応式

HRID 75668 の反応式
[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:14]([NH:15][CH3:16])=[CH:13][C:12](=[O:17])[N:11]([CH3:18])[C:10]1=[O:19].[CH3:20][CH:21]([C:25]([OH:27])=O)[C:22]([OH:24])=O>C(OC(=O)C)(=O)C>[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:14]2[N:15]([CH3:16])[C:25](=[O:27])[C:21]([CH3:20])=[C:22]([OH:24])[C:13]=2[C:12](=[O:17])[N:11]([CH3:18])[C:10]1=[O:19]

参加物

4

反応物 2

HCID 487Methylmalonic AcidHCID 597172291-(2-fluoro-4-iodophenyl)-3-methyl-6-methylamino-1H-pyrimidine-2,4-dione2 回

生成物 1

HCID 597170461-(2-fluoro-4-iodophenyl)-5-hydroxy-3,6,8-trimethyl-1H,8H-pyrido[2,3-d]pyrimidine-2,4,7-trione収率 37.2%

試薬・触媒・溶媒 1

HCID 7918Acetic Anhydride溶媒

反応条件

温度
95 °C

実験手順

To a 6:5 mixture (59.6 g) 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 obtained in Step 4 and 2-methyl-malonic acid 54 (20.7 g) was added acetic anhydride (180 ml), and the mixture was stirred with heating at 95° C. for 1 hr. After allowing to cool to room temperature, the mixture was concentrated under reduced pressure. Tetrahydrofuran (350 ml) was added to the residue, and the mixture was stirred with heating under reflux for 1 hr. After allowing to cool to room temperature, the crystals were filtered off. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography (chloroform:tetrahydrofuran=18:1). Toluene (150 ml) was added to the obtained solid, and the mixture was stirred with heating under reflux for 30 min. After allowing to return to room temperature, the crystals were collected by filtration and dried to give 1-(2-fluoro-4-iodophenyl)-5-hydroxy-3,6,8-trimethyl-1H,8H-pyrido[2,3-d]pyrimidine-2,4,7-trione 69 (27.0 g, yield 37%) as colorless crystals.

後処理

  1. temperatureto cool to room temperature
  2. concentrationthe mixture was concentrated under reduced pressure
  3. additionTetrahydrofuran (350 ml) was added to the residue
  4. stirringthe mixture was stirred
  5. temperaturewith heating
  6. temperatureunder reflux for 1 hr
  7. temperatureto cool to room temperature
  8. filtrationthe crystals were filtered off
  9. concentrationThe filtrate was concentrated under reduced pressure
  10. customthe residue was purified by column chromatography (chloroform:tetrahydrofuran=18:1)
  11. additionToluene (150 ml) was added to the obtained solid
  12. stirringthe mixture was stirred
  13. temperaturewith heating
  14. temperatureunder reflux for 30 min
  15. customto return to room temperature
  16. filtrationthe crystals were collected by filtration
  17. customdried

出典と根拠

ORDレコード
ord-9577eb3228ef4979b6fc677216c0b48c
出典データセット
uspto-grants-2014_09
特許番号
US08835443B2

関連ノート

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