Water → (3-(4-(1H-Pyrazol-1-yl)benzyl)-4-chloro-2-methoxyquinolin-6-yl)(2,4-dimethylthiazol-5-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol

HRID 926587

Reaktionsgleichung

Reaktionsgleichung von HRID 926587
C([Li])CCC.[N:6]1([C:11]2[CH:31]=[CH:30][C:14]([CH2:15][C:16]3[C:17]([O:28][CH3:29])=[N:18][C:19]4[C:24]([C:25]=3[Cl:26])=[CH:23][C:22](Br)=[CH:21][CH:20]=4)=[CH:13][CH:12]=2)[CH:10]=[CH:9][CH:8]=[N:7]1.[CH3:32][C:33]1[S:34][C:35]([C:39]([C:41]2[N:45]([CH3:46])[N:44]=[N:43][CH:42]=2)=[O:40])=[C:36]([CH3:38])[N:37]=1.O>O1CCCC1>[N:6]1([C:11]2[CH:31]=[CH:30][C:14]([CH2:15][C:16]3[C:17]([O:28][CH3:29])=[N:18][C:19]4[C:24]([C:25]=3[Cl:26])=[CH:23][C:22]([C:39]([C:35]3[S:34][C:33]([CH3:32])=[N:37][C:36]=3[CH3:38])([C:41]3[N:45]([CH3:46])[N:44]=[N:43][CH:42]=3)[OH:40])=[CH:21][CH:20]=4)=[CH:13][CH:12]=2)[CH:10]=[CH:9][CH:8]=[N:7]1

Komponenten

6

Edukt 4

HCID 962WaterHCID 867155963-(4-(1H-Pyrazol-1-yl)benzyl)-6-bromo-4-chloro-2-methoxyquinoline2×HCID 86715632(2,4-Dimethylthiazol-5-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanone2×HCID 178418339Butyllithium

Produkt 1

HCID 118006243(3-(4-(1H-Pyrazol-1-yl)benzyl)-4-chloro-2-methoxyquinolin-6-yl)(2,4-dimethylthiazol-5-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
23 °C

Versuchsvorschrift

A solution of n-butyllithium in hexanes (2.5 M, 0.47 mL, 1.2 mmol) was added dropwise to a stirring solution of 3-(4-(1H-pyrazol-1-yl)benzyl)-6-bromo-4-chloro-2-methoxyquinoline (500 mg, 1.2 mmol, Intermediate 10) in tetrahydrofuran (9 mL) at −78° C. After 5 minutes, a solution of (2,4-dimethylthiazol-5-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanone (259 mg, 1.2 mmol, Intermediate 23: step b) in tetrahydrofuran (2 mL) was added dropwise. After 2 minutes, the flask was placed into an ice-water bath. After 90 minutes, water (4 mL) was added and the mixture was allowed to warm to 23° C. The biphasic mixture was partitioned between saturated aqueous sodium chloride solution (20 mL) and ethyl acetate (50 mL). The layers were separated. The organic layer was dried with sodium sulfate and the dried solution was filtered. Silica gel (5 g) was added to the filtrate and the mixture was concentrated by rotary evaporation to afford a free-flowing powder. The powder was loaded onto a silica gel column for flash column chromatography purification. Elution with 40% ethyl acetate-hexanes initially, grading to 90% ethyl acetate-hexanes provided the title compound as an off-white foam. 1H NMR (400 MHz, CDCl3) δ ppm 8.15 (d, J=2.2 Hz, 1H), 7.89-7.81 (m, 2H), 7.67 (d, J=1.7 Hz, 1H), 7.59-7.54 (m, 2H), 7.54-7.48 (m, 1H), 7.41-7.34 (m, 2H), 7.23 (s, 1H), 6.45-6.41 (m, 1H), 4.32 (s, 2H), 4.11 (s, 3H), 3.91 (s, 3H), 3.71 (s, 1H), 2.58 (s, 3H), 2.15 (s, 3H); MS (ESI): mass calcd. for C29H26ClN7O2S, 571.2. m/z found, 572.1 [M+H]+.

Aufarbeitung

  1. waitAfter 2 minutes
  2. customthe flask was placed into an ice-water bath
  3. waitAfter 90 minutes
  4. customThe biphasic mixture was partitioned between saturated aqueous sodium chloride solution (20 mL) and ethyl acetate (50 mL)
  5. customThe layers were separated
  6. dry with materialThe organic layer was dried with sodium sulfate
  7. filtrationthe dried solution was filtered
  8. additionSilica gel (5 g) was added to the filtrate
  9. concentrationthe mixture was concentrated by rotary evaporation
  10. customto afford a free-flowing powder
  11. customThe powder was loaded onto a silica gel column for flash column chromatography purification
  12. washElution with 40% ethyl acetate-hexanes initially

Quellen und Nachweise

ORD-Eintrag
ord-306f681953ca429a91a756e5d85e4754
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09284308B2

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