2,4-Dibromo-1,3-thiazole → 4-((4-Bromothiazol-2-yl)(5-ethoxy-2-fluoro-3-isopropoxyphenyl)methylamino)benzonitrile

HRID 2104957ノート

反応式

HRID 2104957 の反応式
Br[C:2]1[S:3][CH:4]=[C:5]([Br:7])[N:6]=1.[Li]CCCC.[CH2:13]([O:15][C:16]1[CH:17]=[C:18]([O:33][CH:34]([CH3:36])[CH3:35])[C:19]([F:32])=[C:20]([CH:31]=1)/[CH:21]=[N:22]/[C:23]1[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][CH:24]=1)[CH3:14]>C1COCC1>[Br:7][C:5]1[N:6]=[C:2]([N:22]([CH2:21][C:20]2[CH:31]=[C:16]([O:15][CH2:13][CH3:14])[CH:17]=[C:18]([O:33][CH:34]([CH3:36])[CH3:35])[C:19]=2[F:32])[C:23]2[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][CH:24]=2)[S:3][CH:4]=1

参加物

5

反応物 3

HCID 27632972,4-Dibromo-1,3-thiazoleHCID 178418339ButyllithiumHCID 178466720HCID 178466720、化合物

生成物 1

HCID 688133224-((4-Bromothiazol-2-yl)(5-ethoxy-2-fluoro-3-isopropoxyphenyl)methylamino)benzonitrile収率 19.3%

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 a solution of 2,4-dibromothiazole (100 mg, 0.412 mmol) in 2 mL THF was added BuLi (1.6 M in THF, 283 μL, 0.453 mmol). The mixture was stirred at −78° C. for 15 min, then a solution of Intermediate 7.3 (134 mg, 0.412 mmol) in 0.6 mL THF was added dropwise. The mixture was stirred at −78° C. for 30 min, was allowed to warm to rt, then was quenched with sat. NH4Cl. The mixture was diluted with EtOAc, washed with H2O and brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (0 to 40% EtOAc/hexanes gradient) followed by preparative HPLC purification to afford 39 mg of Intermediate 16.1.

後処理

  1. stirringThe mixture was stirred at −78° C. for 30 min
  2. temperatureto warm to rt
  3. customwas quenched with sat. NH4Cl
  4. additionThe mixture was diluted with EtOAc
  5. washwashed with H2O and brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customThe crude product was purified by flash chromatography (0 to 40% EtOAc/hexanes gradient)
  9. customfollowed by preparative HPLC purification

出典と根拠

ORDレコード
ord-09466bdbd88546ce8cb51f4629933834
出典データセット
uspto-grants-2009_08
特許番号
US07576098B2

反応ノート

読み込み中…