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(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(1,2-dimethyl-1H-imidazol-5-yl)methanone → 1-(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)-1-(1,2-dimethyl-1H-imidazol-5-yl)prop-2-yn-1-ol

HRID 526865
ノート
印刷プレビュー

反応式

HRID 526865 の反応式
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([C:14]3[N:18]([CH3:19])[C:17]([CH3:20])=[N:16][CH:15]=3)=[O:13])[CH:10]=2)[N:5]=[C:4]([O:21][CH3:22])[C:3]=1[CH2:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][CH:25]=1.[C-:34]#[C-:35].[Si]([Li])(C)(C)C>C1COCC1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([C:14]3[N:18]([CH3:19])[C:17]([CH3:20])=[N:16][CH:15]=3)([OH:13])[C:34]#[CH:35])[CH:10]=2)[N:5]=[C:4]([O:21][CH3:22])[C:3]=1[CH2:23][C:24]1[CH:25]=[CH:26][C:27]([C:30]([F:31])([F:33])[F:32])=[CH:28][CH:29]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

4

反応物 2

HCID 86715634(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(1,2-dimethyl-1H-imidazol-5-yl)methanone2 回HCID 178462447HCID 178462447、化合物2 回

生成物 1

HCID 1180064811-(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)-1-(1,2-dimethyl-1H-imidazol-5-yl)prop-2-yn-1-ol

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a flask containing (4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(1,2-dimethyl-1H-imidazol-5-yl)methanone (405 mg, 0.85 mmol, Intermediate 8: step b) was added THF (20 mL). The solution was cooled in a dry-ice bath and TMS-lithiumacetylide (0.5 M in Et20, 1.8 mL, 0.9 mmol) was introduced. After 60 minutes, additional TMS-lithiumacetylide (5.0 mL, 2.5 mmol, 0.5 M in Et2O) was added and the reaction mixture was stirred at room temperature overnight. After 24 hours, the reaction was quenched with aqueous NH4Cl solution and the aqueous portion was extracted with EtOAc (4×40 mL). The combined organics were washed with brine, dried over MgSO4, filtered and concentrated. Chromatography on silica gel (2% MeOH-DCM increasing to 5% 2 M NH3-MeOH) afforded the title compound and the silylated title compound. 1H NMR (400 MHz, CDCl3) δ 8.46 (d, J=1.9 Hz, 1H), 7.84-7.68 (m, 2H), 7.44 (dd, J=43.2, 8.2 Hz, 5H), 6.67 (s, 1H), 4.34 (s, 2H), 4.07 (s, 3H), 3.37 (s, 3H), 2.77 (s, 1H), 2.32-2.12 (m, 3H); MS (ESI): mass calcd. for C26H21ClF3N3O2, 499.1, m/z found 500.1 [M+H]+. 1-(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)-1-(1,2-dimethyl-1H-imidazol-5-yl)prop-2-yn-1-ol was purified by chiral chromatography (Chiralpak AD (20 μM) diacel (41 mm×41 mm), heptane:2-propanol with 2% isopropylamine (93:7)) to give 2 enantiomers. The first eluting enantiomer was Example 14b and the second eluting enantiomer was Example 14c.

後処理

  1. temperatureThe solution was cooled in a dry-ice bath
  2. waitAfter 24 hours
  3. customthe reaction was quenched with aqueous NH4Cl solution
  4. extractionthe aqueous portion was extracted with EtOAc (4×40 mL)
  5. washThe combined organics were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated

出典と根拠

ORDレコード
ord-2562251756c04bd78c74e3121de2b662
出典データセット
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09346782B2

反応ノート

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