反応 #1013785

反応方程式

pyridin-2-ylmagnesium bromide

(3-(benzo[b]thiophen-2-ylmethyl)-4-chloro-2-methoxyquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanone

Intermediate 40

(3-(benzo[b]thiophen-2-ylmethyl)-4-chloro-2-methoxyquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanone

→

title compound

(3-(Benzo[b]thiophen-2-ylmethyl)-4-chloro-2-methoxyquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)(pyridin-2-yl)methanol

溶媒

THF

反応条件

後処理

1. 1
   温度the solution was cooled in an ice bath
2. 2
   その他quenched with saturated aqueous ammonium chloride
3. 3
   その他removed from the cold bath
4. 4
   その他The mixture was partitioned between water and ethyl acetate
5. 5
   抽出The separated aqueous phase was further extracted with ethyl acetate
6. 6
   乾燥The organic phase was dried (Na2SO4)
7. 7
   ろ過filtered
8. 8
   濃縮concentrated to dryness
9. 9
   その他The crude product was purified by flash column chromatography (silica gel, 0-5% MeOH-DCM)
10. 10
    抽出extracted with DCM
11. 11
    乾燥dried (Na2SO4)
12. 12
    ろ過filtered
13. 13
    濃縮concentrated to dryness

実験手順

LaCl3-2LiCl (0.6 M in THF, 0.78 mL, 0.47 mmol) was added dropwise by syringe to a solution of (3-(benzo[b]thiophen-2-ylmethyl)-4-chloro-2-methoxyquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanone (101.4 mg, 0.226 mmol, Intermediate 40: step b) in dry THF (2 mL). After 5 minutes, the solution was cooled in an ice bath and pyridin-2-ylmagnesium bromide (2.8 mL, 0.7 mmol) was added dropwise via syringe. The reaction was stirred for 3 hours, then quenched with saturated aqueous ammonium chloride and removed from the cold bath. 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 to dryness. The crude product was purified by flash column chromatography (silica gel, 0-5% MeOH-DCM) followed by reverse-phase chromatography (acetonitrile/H2O+0.05% TFA). The isolated product fractions were basified with saturated aqueous sodium bicarbonate, extracted with DCM, dried (Na2SO4), filtered, and concentrated to dryness to provide the title compound. 1H NMR (400 MHz, CDCl3) δ ppm 8.63-8.59 (m, 1H), 8.13 (d, J=2.0 Hz, 1H), 7.82 (d, J=8.7 Hz, 1H), 7.71-7.60 (m, 4H), 7.49 (d, J=1.1 Hz, 1H), 7.30-7.18 (m, 4H), 7.08 (d, J=1.0 Hz, 1H), 6.32 (d, J=1.1 Hz, 1H), 4.50 (d, J=1.1 Hz, 2H), 4.13 (s, 3H), 3.41 (s, 3H); MS m/e 527.2 [M+H]+.

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