4-Bromo-2-fluoroaniline → 4-(4-Bromo-2-fluoro-phenylamino)-6-chloro-pyridazine-3-carboxylic acid

HRID 558224ノート

反応式

HRID 558224 の反応式
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[C:4]([F:9])[CH:3]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.Cl[C:21]1[CH:26]=[C:25]([Cl:27])[N:24]=[N:23][C:22]=1[C:28]([OH:30])=[O:29]>C1COCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:21]2[CH:26]=[C:25]([Cl:27])[N:24]=[N:23][C:22]=2[C:28]([OH:30])=[O:29])=[C:4]([F:9])[CH:3]=1

参加物

5

反応物 3

HCID 1230504-Bromo-2-fluoroanilineHCID 2733832Lithium HexamethyldisilazideHCID 219192804,6-Dichloro-3-pyridazinecarboxylic acid

生成物 1

HCID 595194954-(4-Bromo-2-fluoro-phenylamino)-6-chloro-pyridazine-3-carboxylic acid

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

To the stirred solution of 4-bromo-2-fluorophenylamine (3.15 g, 16.58 mmol) in THF (50 ml) under argon at −78° C. is added dropwise LiHMDS (24.9 ml, 24.9 mmol, 1.0 M in hexane). After stirring for one hour at −78° C., a solution of 4,6-dichloropyridazine-3-carboxylic acid (1.6 g, 8.29 mmol) in THF (10 ml) is added dropwise. The resulting mixture is allowed to warm to room temperature slowly and was stirred continuously for 18 hours. The reaction is quenched by addition of 5 ml of water, diluted with ethyl acetate, acidified with aqueous 1.0 M HCl to pH 1-2. The layers are separated and aqueous layer is extracted with ethyl acetate (30 ml×3). The combined organic layers are washed with brine (30 ml×3), dried over Na2SO4, and concentrated under reduced pressure. The residue is purified by flash column chromatography to give the product.

後処理

  1. temperatureto warm to room temperature slowly
  2. stirringwas stirred continuously for 18 hours
  3. customThe reaction is quenched by addition of 5 ml of water
  4. additiondiluted with ethyl acetate
  5. customThe layers are separated
  6. extractionaqueous layer is extracted with ethyl acetate (30 ml×3)
  7. washThe combined organic layers are washed with brine (30 ml×3)
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated under reduced pressure
  10. customThe residue is purified by flash column chromatography
  11. customto give the product

出典と根拠

ORDレコード
ord-22b6b66699f3481ba2455eadc5822753
出典データセット
uspto-grants-2011_11
特許番号
US08063049B2

反応ノート

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