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

HRID 526852노트

반응식

HRID 526852 반응식
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

참가 물질

5

반응물 3

HCID 27348955-Bromo-2-methoxypyridineHCID 86716078(2,4-Dichloro-3-phenylquinolin-6-yl)(3-methylisoxazol-5-yl)methanone2회HCID 178418339Butyllithium

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
-78 °C

실험 절차

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)+.

후처리

  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)

출처 및 근거

ORD 기록
ord-02c482ec443c404fb2913ad428a788f3
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346782B2

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