5-Bromo-2-methoxypyridine → (2,4-Dichloro-3-phenylquinolin-6-yl)(6-methoxypyridin-3-yl)(3-methylisoxazol-5-yl)methanol

HRID 526852ノート

反応式

HRID 526852 の反応式
Br[C:2]1[CH:3]=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1.[Cl:10][C:11]1[C:20]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[C:19]([Cl:27])[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([C:28]([C:30]3[O:34][N:33]=[C:32]([CH3:35])[CH:31]=3)=[O:29])[CH:17]=2)[N:12]=1.[Li]CCCC>C1COCC1>[Cl:10][C:11]1[C:20]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[C:19]([Cl:27])[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([C:28]([C:2]3[CH:7]=[N:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=3)([C:30]3[O:34][N:33]=[C:32]([CH3:35])[CH:31]=3)[OH:29])[CH:17]=2)[N:12]=1

参加物

5

反応物 3

HCID 27348955-Bromo-2-methoxypyridineHCID 86716078(2,4-Dichloro-3-phenylquinolin-6-yl)(3-methylisoxazol-5-yl)methanone2 回HCID 178418339Butyllithium

生成物 1

HCID 117869477(2,4-Dichloro-3-phenylquinolin-6-yl)(6-methoxypyridin-3-yl)(3-methylisoxazol-5-yl)methanol

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-78 °C

実験手順

5-Bromo-2-methoxypyridine (0.019 mL, 0.15 mmol) was added to a solution of (2,4-dichloro-3-phenylquinolin-6-yl)(3-methylisoxazol-5-yl)methanone (44.1 mg, 0.115 mmol, Intermediate 3: step b) in THF (1 mL) under a nitrogen atmosphere. The mixture was cooled to −78° C. and n-BuLi (1.6 M in hexane, 0.094 mL, 0.150 mmol) was added dropwise. The mixture was stirred at −78° C. for 30 minutes, then moved to an ice bath and stirred for 30 minutes. The reaction was quenched by addition of saturated aqueous NH4Cl and was diluted with water. The mixture was extracted three times with EtOAc. The organic phase was dried (Na2SO4), filtered, and concentrated to dryness. The crude product was purified by RP-HPLC (10-90% CH3CN—H2O, 0.1% TFA) to afford the title compound along with the intended product (2,4-dichloro-3-phenylquinolin-6-yl)(6-methoxypyridin-3-yl)(3-methylisoxazol-5-yl)methanol. 1H NMR (400 MHz, DMSO-d6) δ 8.41 (s, 1H), 8.06 (d, J=8.80 Hz, 1H), 7.93 (d, J=8.80 Hz, 1H), 7.47-7.60 (m, 3H), 7.38-7.47 (m, 2H), 6.55 (br. s., 1H), 6.33 (s, 1H), 2.22-2.36 (m, 2H), 2.20 (s, 3H), 1.17-1.36 (m, 3H), 0.92-1.10 (m, 1H), 0.81 (t, J=6.97 Hz, 3H); MS m/e 441.1 (M+H)+.

後処理

  1. custommoved to an ice bath
  2. stirringstirred for 30 minutes
  3. customThe reaction was quenched by addition of saturated aqueous NH4Cl
  4. additionwas diluted with water
  5. extractionThe mixture was extracted three times with EtOAc
  6. dry with materialThe organic phase was dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated to dryness
  9. customThe crude product was purified by RP-HPLC (10-90% CH3CN—H2O, 0.1% TFA)

出典と根拠

ORDレコード
ord-02c482ec443c404fb2913ad428a788f3
出典データセット
uspto-grants-2016_05
特許番号
US09346782B2

反応ノート

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