Water → 6-[4-(4-Chloro-benzylsulfanyl)-3,5-dimethyl-pyrazol-1-yl]-[2,2']bipyridinyl

HRID 1410383Notes

Reaction equation

HRID 1410383 reaction equation
[Cl:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][S:7][C:8]2[C:9]([CH3:14])=[N:10][NH:11][C:12]=2[CH3:13])=[CH:4][CH:3]=1.[H-].[Na+].Br[C:20]1[N:25]=[C:24]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=2)[CH:23]=[CH:22][CH:21]=1.O>COCCOCCOC>[Cl:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][S:7][C:8]2[C:12]([CH3:13])=[N:11][N:10]([C:28]3[N:27]=[C:26]([C:24]4[CH:23]=[CH:22][CH:21]=[CH:20][N:25]=4)[CH:31]=[CH:30][CH:29]=3)[C:9]=2[CH3:14])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 117911522-Bromo-6-(pyridin-2-yl)pyridineHCID 221748524-(4-chloro-benzylsulfanyl)-3,5-dimethyl-1H-pyrazole

Product 1

HCID 221748586-[4-(4-Chloro-benzylsulfanyl)-3,5-dimethyl-pyrazol-1-yl]-[2,2']bipyridinylYield 43%

Reagents, catalysts & solvents 1

HCID 8150DiglymeSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 4-(4-chloro-benzylsulfanyl)-3,5-dimethyl-1H-pyrazole (0.708 g, 2.80 mmol) in 2-methoxyethyl ether (7 mL) was added sodium hydride (0.123 g (60% dispersion), 3.08 mmol). After stirring for 5 minutes, 6-bromo-[2,2′]bipyridinyl (0.691 g, 2.94 mmol) was added, and the reaction mixture was heated to 100° C. for 16 hours. The reaction mixture was allowed to cool to room temperature, and water (100 mL) was added. The suspension was extracted with ethyl acetate (50 mL×2), and the combined organic extracts washed with brine (100 mL). The organic phase was dried (magnesium sulfate), filtered, and concentrated to afford a tan solid. Flash chromatography over silica (methanol/methylene chloride) followed by recrystallization from aqueous methanol provided 0.485 g (43%) of the product as a white solid: 1H NMR (CDCl3) δ 8.70-8.68 (m, 1H), 8.34 (d, J=7.9 Hz, 1H), 8.29 (d, J=7.9 Hz, 1H), 7.94 (t, J=7.9 Hz, 1H), 7.86 (dt, J=2.0, 7.9 Hz, 2H), 7.35-7.31 (m, 1H), 7.22 (d, J=8.3 Hz, 2H), 6.99 (d, J=8.3 Hz, 2H), 3.65 (s, 2H), 2.45 (s, 3H), 2.21 (s, 3H) ppm. 13C NMR (CDCl3) δ 155.7, 154.5, 153.8, 152.9, 149.5, 145.9, 139.7, 137.3, 137.2, 133.1, 130.7, 128.7, 124.2, 121.3, 118.5, 116.1, 110.0, 40.3, 13.6, 12.3 ppm.

Workup

  1. temperatureto cool to room temperature
  2. extractionThe suspension was extracted with ethyl acetate (50 mL×2)
  3. washthe combined organic extracts washed with brine (100 mL)
  4. dry with materialThe organic phase was dried (magnesium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto afford a tan solid
  8. customFlash chromatography over silica (methanol/methylene chloride) followed by recrystallization from aqueous methanol

Sources & evidence

ORD record
ord-e362796abd854ad09d0fa822a69b53bf
Source dataset
uspto-grants-2014_12
Patent number
US08921547B2

Reaction notes

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