Water → (3-(4-(1H-Pyrazol-1-yl)benzyl)-4-chloro-2-methoxyquinolin-6-yl)(1,2-dimethyl-1H-imidazol-5-yl)methanol

HRID 926479ノート

反応式

HRID 926479 の反応式
C([Li])CCC.[N:6]1([C:11]2[CH:31]=[CH:30][C:14]([CH2:15][C:16]3[C:17]([O:28][CH3:29])=[N:18][C:19]4[C:24]([C:25]=3[Cl:26])=[CH:23][C:22](Br)=[CH:21][CH:20]=4)=[CH:13][CH:12]=2)[CH:10]=[CH:9][CH:8]=[N:7]1.[CH3:32][N:33]1[C:37]([CH:38]=[O:39])=[CH:36][N:35]=[C:34]1[CH3:40].O>O1CCCC1>[N:6]1([C:11]2[CH:31]=[CH:30][C:14]([CH2:15][C:16]3[C:17]([O:28][CH3:29])=[N:18][C:19]4[C:24]([C:25]=3[Cl:26])=[CH:23][C:22]([CH:38]([C:37]3[N:33]([CH3:32])[C:34]([CH3:40])=[N:35][CH:36]=3)[OH:39])=[CH:21][CH:20]=4)=[CH:13][CH:12]=2)[CH:10]=[CH:9][CH:8]=[N:7]1

参加物

6

反応物 4

HCID 962WaterHCID 31596101,2-dimethyl-1H-imidazole-5-carbaldehydeHCID 867155963-(4-(1H-Pyrazol-1-yl)benzyl)-6-bromo-4-chloro-2-methoxyquinoline2 回HCID 178418339Butyllithium

生成物 1

HCID 118005895(3-(4-(1H-Pyrazol-1-yl)benzyl)-4-chloro-2-methoxyquinolin-6-yl)(1,2-dimethyl-1H-imidazol-5-yl)methanol

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
23 °C

実験手順

A solution of n-butyllithium in hexanes (1.6 M, 1.5 mL, 2.3 mmol) was added dropwise to a stirring solution of 3-(4-(1H-pyrazol-1-yl)benzyl)-6-bromo-4-chloro-2-methoxyquinoline (1 g, 2.3 mmol, Intermediate 10) in tetrahydrofuran (18 mL) at −78° C. After 3 minutes, a solution of 1,2-dimethyl-1H-imidazole-5-carbaldehyde (347 mg, 2.8 mmol) in tetrahydrofuran (5 mL) was added dropwise. After 5 minutes, the flask was placed into an ice-water bath. After 30 minutes, water (10 mL) was added and the biphasic mixture was allowed to warm to 23° C. The mixture was partitioned between half-saturated sodium chloride solution (50 mL) and ethyl acetate (100 mL). The layers were separated. The organic layer was dried with sodium sulfate and the dried solution was filtered. Silica gel (3 g) was added to the filtrate and the solvent was removed by rotary evaporation to afford a free-flowing powder. The powder was loaded onto a column of silica gel for purification. Elution with ethyl acetate initially, grading to 7% methanol-ethyl acetate provided the title compound as an off-white solid.

後処理

  1. waitAfter 5 minutes
  2. customthe flask was placed into an ice-water bath
  3. waitAfter 30 minutes
  4. customThe mixture was partitioned between half-saturated sodium chloride solution (50 mL) and ethyl acetate (100 mL)
  5. customThe layers were separated
  6. dry with materialThe organic layer was dried with sodium sulfate
  7. filtrationthe dried solution was filtered
  8. additionSilica gel (3 g) was added to the filtrate
  9. customthe solvent was removed by rotary evaporation
  10. customto afford a free-flowing powder
  11. customThe powder was loaded onto a column of silica gel for purification
  12. washElution with ethyl acetate initially

出典と根拠

ORDレコード
ord-ff25b25dc64e4608bc549df76fff9c91
出典データセット
uspto-grants-2016_03
特許番号
US09284308B2

反応ノート

読み込み中…