(2,4-Dichloro-pyrimidin-5-yl-methyl)-(2-fluoro-4-methoxy-phenyl)amine → HCID 178491935、化合物

HRID 1243183ノート

反応式

HRID 1243183 の反応式
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([CH2:9][NH:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][C:12]=2[F:19])=[CH:4][N:3]=1.C([Li])CCC.[C:25]([Si:29]([O:32][C@H:33]1[CH2:38][CH2:37][C@H:36]([N:39]=[C:40]=[O:41])[CH2:35][CH2:34]1)([CH3:31])[CH3:30])([CH3:28])([CH3:27])[CH3:26]>O1CCCC1.C(OCC)(=O)C>[C:25]([Si:29]([CH3:31])([CH3:30])[O:32][C@H:33]1[CH2:38][CH2:37][C@H:36]([N:39]2[C:6]3=[N:7][C:2]([Cl:1])=[N:3][CH:4]=[C:5]3[CH2:9][N:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][C:12]=3[F:19])[C:40]2=[O:41])[CH2:35][CH2:34]1)([CH3:28])([CH3:27])[CH3:26]

参加物

6

反応物 3

HCID 21939275(2,4-Dichloro-pyrimidin-5-yl-methyl)-(2-fluoro-4-methoxy-phenyl)amineHCID 178418339ButyllithiumHCID 178455365HCID 178455365、化合物

生成物 1

HCID 178491935HCID 178491935、化合物

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
-78 °C

実験手順

To a solution of (2,4-dichloro-pyrimidin-5-yl-methyl)-(2-fluoro-4-methoxy-phenyl)amine (1.1 g, 3.64 mmol) (from Example 17a supra) in tetrahydrofuran (50 mL) at −78° C. was added n-butyllithium (2.5 M in hexanes, 1.75 mL, 4.37 mmol) (Aldrich). After stirring at −78° C. for 40 minutes, tert-butyl-(trans-4-isocyanato-cyclohexyloxy)-dimethyl-silane (1.12 g, 4.37 mmol) (from Example 17b supra) was added. The mixture was stirred at −70° C. for 1 hour and then at room temperature for 3 hours. It was diluted with ethyl acetate, washed with brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography eluting with ethyl acetate-hexanes (3:7 then 2:3) to give 1-[trans-4-(tert-butyl-dimethyl-silanyloxy)-cyclohexyl]-7-chloro-3-(2-fluoro-4-methoxy-phenyl)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one. (Yield 0.60 g, 33%).

後処理

  1. stirringThe mixture was stirred at −70° C. for 1 hour
  2. waitat room temperature for 3 hours
  3. washwashed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash chromatography
  8. washeluting with ethyl acetate-hexanes (3:7

出典と根拠

ORDレコード
ord-e438cd5c9fff4ae2b58442a950fdcb26
出典データセット
uspto-grants-2006_10
特許番号
US07115740B2

反応ノート

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