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Tetrahydrofuran → (1-Methyl-1H-imidazol-5-yl)(3-phenyl-2,4-bis(trifluoromethyl)quinolin-6-yl)(pyridin-2-yl)methanol

HRID 627572
ノート
印刷プレビュー

反応式

HRID 627572 の反応式
[Li]CCCC.Br[C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[N:13]=[C:12]([C:17]([F:20])([F:19])[F:18])[C:11]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[C:10]2[C:27]([F:30])([F:29])[F:28].CC(S(N=[C:38]([C:45]1[N:49]([CH3:50])[CH:48]=[N:47][CH:46]=1)[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][N:40]=1)=O)(C)C.C1C[O:54]CC1>>[CH3:50][N:49]1[C:45]([C:38]([C:7]2[CH:8]=[C:9]3[C:14](=[CH:15][CH:16]=2)[N:13]=[C:12]([C:17]([F:20])([F:19])[F:18])[C:11]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[C:10]3[C:27]([F:30])([F:29])[F:28])([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][N:40]=2)[OH:54])=[CH:46][N:47]=[CH:48]1
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 4

HCID 8028Tetrahydrofuran2 回HCID 867160666-Bromo-3-phenyl-2,4-bis(trifluoromethyl)quinoline2 回HCID 867161542-methyl-N-((1-methyl-1H-imidazol-5-yl)(pyridin-2-yl)methylene)propane-2-sulfinamide2 回HCID 178418339Butyllithium

生成物 1

HCID 86716153(1-Methyl-1H-imidazol-5-yl)(3-phenyl-2,4-bis(trifluoromethyl)quinolin-6-yl)(pyridin-2-yl)methanol

実験手順

A solution of n-BuLi (2.5 M in hexanes, 0.10 mL, 0.25 mmol) was added dropwise by syringe to a solution of 6-iodo-3-phenyl-2,4-bis(trifluoromethyl)quinoline (122 mg, 0.261 mmol, Intermediate 8, step d) in dry THF (4.5 mL) in a dry ice-acetone bath. After 2 min, a solution of (1-methyl-1H-imidazol-5-yl)(pyridin-2-yl)methanone (0.0540 g, 0.288 mmol, Intermediate 11, step b) in dry THF (0.25 mL) was added dropwise. The reaction mixture was stirred for 5 min in a dry ice-acetone bath, then the reaction flask was placed into an ice-water bath. After 5 min, the mixture was warmed to room temperature and the reaction was quenched with methanol and water. 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 reverse-phase chromatography (acetonitrile w/0.05% TFA in water). Saturated sodium bicarbonate was used to form the free-base product, which was extracted with DCM and concentrated to provide the title compound as a white solid. 1H NMR (500 MHz, CDCl3) δ 8.66 (d, J=4.4 Hz, 1H), 8.32 (d, J=8.9 Hz, 1H), 8.26 (d, J=2.0 Hz, 1H), 8.05 (dd, J=8.9, 1.8 Hz, 1H), 7.75 (td, J=7.7, 1.7 Hz, 1H), 7.51 (s, 1H), 7.49-7.40 (m, 3H), 7.35 (dd, J=7.0, 5.3 Hz, 1H), 7.28 (s, 1H), 7.22 (d, J=7.9 Hz, 1H), 6.72 (s, 1H), 6.39 (s, 1H), 3.44 (s, 3H). MS m/e 529.2 [M+H]+.

後処理

  1. customthe reaction flask was placed into an ice-water bath
  2. waitAfter 5 min
  3. customthe reaction was quenched with methanol and water
  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 reverse-phase chromatography (acetonitrile w/0.05% TFA in water)
  10. customto form the free-base product, which
  11. extractionwas extracted with DCM
  12. concentrationconcentrated

出典と根拠

ORDレコード
ord-ac6985d688dd495e87b96a27031b7fe2
出典データセット
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09309222B2

反応ノート

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