(2,6-Dimethylpyridin-3-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanone → (4-Chloro-2-methoxy-3-((6-(trifluoromethyl)pyridin-3-yl)methyl)quinolin-6-yl)(2,6-dimethylpyridin-3-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol

HRID 926595

반응식

HRID 926595 반응식
[Li]CCCC.[Cl:6][C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14](C(C3N(C)C(C)=NC=3)O)[CH:15]=2)[N:10]=[C:9]([O:26][CH3:27])[C:8]=1[CH2:28][C:29]1[CH:30]=[N:31][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:33][CH:34]=1.[CH3:39][C:40]1[C:45]([C:46]([C:48]2[N:52]([CH3:53])[N:51]=[N:50][CH:49]=2)=[O:47])=[CH:44][CH:43]=[C:42]([CH3:54])[N:41]=1>C1COCC1>[Cl:6][C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:46]([C:45]3[C:40]([CH3:39])=[N:41][C:42]([CH3:54])=[CH:43][CH:44]=3)([C:48]3[N:52]([CH3:53])[N:51]=[N:50][CH:49]=3)[OH:47])[CH:15]=2)[N:10]=[C:9]([O:26][CH3:27])[C:8]=1[CH2:28][C:29]1[CH:30]=[N:31][C:32]([C:35]([F:36])([F:38])[F:37])=[CH:33][CH:34]=1

참가 물질

5

반응물 3

HCID 86715642(2,6-Dimethylpyridin-3-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanone2회HCID 118005815(4-Chloro-2-methoxy-3-((6-(trifluoromethyl)pyridin-3-yl)methyl)quinolin-6-yl)(1,2-dimethyl-1H-imidazol-5-yl)methanol2회HCID 178418339Butyllithium

생성물 1

HCID 118006333(4-Chloro-2-methoxy-3-((6-(trifluoromethyl)pyridin-3-yl)methyl)quinolin-6-yl)(2,6-dimethylpyridin-3-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

A solution of n-BuLi (2.5 M in hexanes, 0.68 mL, 1.7 mmol) was added dropwise by syringe to a solution of 6-bromo-4-chloro-2-methoxy-3-((6-(trifluoromethyl)pyridin-3-yl)methyl)quinoline (0.404 g, 0.936 mmol, Intermediate 45: step d) in dry THF (17 mL) in a dry ice-acetone bath. After 1-2 minutes, a solution of (2,6-dimethylpyridin-3-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanone (0.346 g, 1.601 mmol, Intermediate 19: step b) in dry THF (8 mL) was added dropwise. The reaction was stirred for 10 minutes, then was moved into an ice bath and allowed to warm to ambient temperature. The reaction was quenched with saturated aqueous ammonium chloride. The mixture was partitioned between water and dichloromethane. The separated aqueous phase was further extracted with dichloromethane. The organic phase was dried (Na2SO4), filtered, and concentrated. The crude product was purified by flash column chromatography (silica gel, 0-4% MeOH-DCM) to provide the title compound. 1H NMR (400 MHz, CDCl3) δ 8.71 (d, J=1.7 Hz, 1H), 8.11 (d, J=2.1 Hz, 1H), 7.80 (d, J=8.7 Hz, 1H), 7.76 (dd, J=8.1, 1.6 Hz, 1H), 7.56 (d, J=8.0 Hz, 1H), 7.40 (dd, J=8.8, 2.2 Hz, 1H), 6.96-6.90 (m, 2H), 6.83 (s, 1H), 5.01 (s, 1H), 4.33 (s, 2H), 4.09 (s, 3H), 3.91 (s, 3H), 2.51 (s, 3H), 2.32 (s, 3H); MS m/e 569.0 [M+H]+.

후처리

  1. customwas moved into an ice bath
  2. customThe reaction was quenched with saturated aqueous ammonium chloride
  3. customThe mixture was partitioned between water and dichloromethane
  4. extractionThe separated aqueous phase was further extracted with dichloromethane
  5. dry with materialThe organic phase was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by flash column chromatography (silica gel, 0-4% MeOH-DCM)

출처 및 근거

ORD 기록
ord-7f7a9a1e9f39448d8cbf9e6fa04053b9
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09284308B2

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