(3,4-Dimethoxyphenyl)(pyridin-3-yl)methanone → (3-(4-(1H-Pyrazol-1-yl)benzyl)-4-chloro-2-methoxyquinolin-6-yl)(3,4-dimethoxyphenyl)(pyridin-3-yl)methanol

HRID 926648

反応式

HRID 926648 の反応式
[Li]CCCC.[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][O:33][C:34]1[CH:35]=[C:36]([C:42]([C:44]2[CH:45]=[N:46][CH:47]=[CH:48][CH:49]=2)=[O:43])[CH:37]=[CH:38][C:39]=1[O:40][CH3:41]>C1COCC1>[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]([C:42]([C:36]3[CH:37]=[CH:38][C:39]([O:40][CH3:41])=[C:34]([O:33][CH3:32])[CH:35]=3)([C:44]3[CH:45]=[N:46][CH:47]=[CH:48][CH:49]=3)[OH:43])=[CH:21][CH:20]=4)=[CH:13][CH:12]=2)[CH:10]=[CH:9][CH:8]=[N:7]1

参加物

5

反応物 3

HCID 15077853(3,4-Dimethoxyphenyl)(pyridin-3-yl)methanone2 回HCID 867155963-(4-(1H-Pyrazol-1-yl)benzyl)-6-bromo-4-chloro-2-methoxyquinoline2 回HCID 178418339Butyllithium

生成物 1

HCID 74220682(3-(4-(1H-Pyrazol-1-yl)benzyl)-4-chloro-2-methoxyquinolin-6-yl)(3,4-dimethoxyphenyl)(pyridin-3-yl)methanol

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

A solution of n-BuLi (2.5 M in hexanes, 0.05 mL, 0.125 mmol) was added dropwise by syringe to a solution of 3-(4-(1H-pyrazol-1-yl)benzyl)-6-bromo-4-chloro-2-methoxyquinoline (32.9 mg, 0.135 mmol, Intermediate 10) in dry THF (2 mL) in a dry ice-acetone bath. After 5 minutes, a solution of (3,4-dimethoxyphenyl)(pyridin-3-yl)methanone (32.9 mg, 0.135 mmol, Intermediate 88: step b) in dry THF (0.2 mL) was added dropwise. The reaction mixture was stirred for 5 minutes in a dry ice-acetone bath, then the reaction flask was placed into an ice-water bath. After 10 minutes, the mixture was warmed to room temperature and the reaction was quenched with saturated ammonium chloride. The mixture was partitioned between water and ethyl acetate. The separated aqueous phase was further extracted with ethyl acetate. The organic phase was dried (Na2SO4), filtered, and concentrated. The crude product was purified by flash column chromatography (silica gel, 20-100% EtOAc-Hexanes) to provide the title compound as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 8.61 (d, J=1.8 Hz, 1H), 8.53 (dd, J=4.8, 1.6 Hz, 1H), 8.10 (d, J=2.0 Hz, 1H), 7.85 (d, J=2.4 Hz, 1H), 7.79 (d, J=8.8 Hz, 1H), 7.69 (dt, J=8.0, 2.0 Hz, 2H), 7.57-7.52 (m, 3H), 7.35 (d, J=8.6 Hz, 2H), 7.29-7.25 (m, 1H), 6.91 (d, J=2.2 Hz, 1H), 6.79 (d, J=8.5 Hz, 1H), 6.66 (dd, J=8.4, 2.2 Hz, 1H), 6.44-6.42 (m, 1H), 4.31 (s, 2H), 4.08 (s, 3H), 3.88 (s, 3H), 3.76 (s, 3H); MS m/e 593.2 [M+H]+.

後処理

  1. customthe reaction flask was placed into an ice-water bath
  2. waitAfter 10 minutes
  3. customthe reaction was quenched with saturated ammonium chloride
  4. customThe mixture was partitioned between water and ethyl acetate
  5. extractionThe separated aqueous phase was further extracted with ethyl acetate
  6. dry with materialThe organic phase was dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by flash column chromatography (silica gel, 20-100% EtOAc-Hexanes)

出典と根拠

ORDレコード
ord-48724a25aecb47bea020d8af116967b9
出典データセット
uspto-grants-2016_03
特許番号
US09284308B2

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