Barbituric Acid → (2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(1-methyl-1H-1,2,4-triazol-5-yl)-2,4,4a,6-tetrahydro-1H,1'H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5'-pyrimidine]-2',4',6'(3'H)-trione

HRID 245574ノート

反応式

HRID 245574 の反応式
[CH3:1][C@@H:2]1[CH2:7][N:6]([C:8]2[C:22]([CH:23]=O)=[CH:21][C:11]3[C:12]([C:15]4[N:19]([CH3:20])[N:18]=[CH:17][N:16]=4)=[N:13][O:14][C:10]=3[C:9]=2[F:25])[CH2:5][C@@H:4]([CH3:26])[O:3]1.[NH:27]1[C:32](=[O:33])[CH2:31][C:30](=[O:34])[NH:29][C:28]1=[O:35]>CO>[F:25][C:9]1[C:10]2[O:14][N:13]=[C:12]([C:15]3[N:19]([CH3:20])[N:18]=[CH:17][N:16]=3)[C:11]=2[CH:21]=[C:22]2[C:8]=1[N:6]1[CH2:5][C@@H:4]([CH3:26])[O:3][C@@H:2]([CH3:1])[C@@H:7]1[C:31]1([C:30](=[O:34])[NH:29][C:28](=[O:35])[NH:27][C:32]1=[O:33])[CH2:23]2

参加物

4

反応物 2

HCID 6211Barbituric AcidHCID 86658124HCID 86658124、化合物2 回

生成物 1

HCID 67433769(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(1-methyl-1H-1,2,4-triazol-5-yl)-2,4,4a,6-tetrahydro-1H,1'H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5'-pyrimidine]-2',4',6'(3'H)-trione

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

反応条件

温度
150 °C

実験手順

A mixture of 6-((2R,6R)-2,6-dimethylmorpholino)-7-fluoro-3-(1-methyl-1H-1,2,4-triazol-5-yl)benzo[d]isoxazole-5-carbaldehyde (Intermediate 537, 124 mg, 0.35 mmol) and pyrimidine-2,4,6(1H,3H,5H)-trione (44.2 mg, 0.35 mmol) in methanol (3 ml) was heated at 150° C. for 1 hour in a microwave reactor. Solvent was removed and the residue was purified by reverse phase HPLC (CH3CN/water gradient with 0.1% TFA). The solid was taken up in 9:1 CH2Cl2— MeOH and washed with NaHCO3 and brine. The aqueous layers were repeatedly extracted with additional 9:1 CH2Cl2-MeOH with each extract being washed with brine. The combined organic layers were dried (MgSO4) and concentrated and the residue was dissolved in THF. After removal of solvent, the solid residue was dried in vacuo at 50° C. overnight to afford desired product.

後処理

  1. customSolvent was removed
  2. customthe residue was purified by reverse phase HPLC (CH3CN/water gradient with 0.1% TFA)
  3. washwashed with NaHCO3 and brine
  4. extractionThe aqueous layers were repeatedly extracted with additional 9:1 CH2Cl2-MeOH with each extract
  5. washbeing washed with brine
  6. dry with materialThe combined organic layers were dried (MgSO4)
  7. concentrationconcentrated
  8. dissolutionthe residue was dissolved in THF
  9. customAfter removal of solvent
  10. customthe solid residue was dried in vacuo at 50° C. overnight

出典と根拠

ORDレコード
ord-58df17934f9345ae863a3662aa71f401
出典データセット
uspto-grants-2014_02
特許番号
US08658641B2

反応ノート

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