Pyrazole → (S)-cyclopropyl(2-methyl-5-phenoxy-6-(1H-pyrazol-1-yl)-3,4-dihydroquinolin-1 (2H)-yl)methanone

HRID 1051721Notes

Reaction equation

HRID 1051721 reaction equation
Br[C:2]1[C:3]([O:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([C:12]([CH:14]1[CH2:16][CH2:15]1)=[O:13])[C@@H:7]([CH3:17])[CH2:6][CH2:5]2.[NH:25]1[CH:29]=[CH:28][CH:27]=[N:26]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.O.[Cu-]=O>[CH:14]1([C:12]([N:8]2[C:9]3[C:4](=[C:3]([O:18][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[C:2]([N:25]4[CH:29]=[CH:28][CH:27]=[N:26]4)=[CH:11][CH:10]=3)[CH2:5][CH2:6][C@@H:7]2[CH3:17])=[O:13])[CH2:16][CH2:15]1

Participants

7

Reactant 3

HCID 1048PyrazoleHCID 10796Cesium carbonateHCID 118086215(S)-(6-bromo-2-methyl-5-phenoxy-3,4-dihydroquinolin-1(2H)-yl)(cyclopropyl)methanone

Product 1

HCID 118076281(S)-cyclopropyl(2-methyl-5-phenoxy-6-(1H-pyrazol-1-yl)-3,4-dihydroquinolin-1 (2H)-yl)methanoneYield 17.2%

Reagents, catalysts & solvents 3

HCID 178419072HCID 178419072, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (S)-(6-bromo-2-methyl-5-phenoxy-3,4-dihydroquinolin-1 (2H)-yl)(cyclopropyl)methanone (0.300 g, 0.78 mmol), 1H-pyrazole (0.053 g, 0.78 mmol), copper (I) oxide (0.056 g, 0.39 mmol), cesium carbonate (0.508 g, 1.56 mmol) in N,N-dimethylformamide (5 mL) stirred for 18 h at 100° C. The resulting mixture was cooled to room temperature, diluted with water (20 mL) and extracted with ethyl acetate (3×20 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified via preparative thin layer chromatography (eluting with 1:10, ethyl acetate/petroleum ether) to afford (S)-cyclopropyl(2-methyl-5-phenoxy-6-(1H-pyrazol-1-yl)-3,4-dihydroquinolin-1 (2H)-yl)methanone (0.050 g, 17%) as a yellow solid. MS (ESI, pos. ion) m/z 374 [M+H]+.

Workup

  1. temperatureThe resulting mixture was cooled to room temperature
  2. extractionextracted with ethyl acetate (3×20 mL)
  3. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified via preparative thin layer chromatography (eluting with 1:10, ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-0bd3c9f9c7414fd996e06d48b392b13a
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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