Sodium Iodide → N'-[3-tert-butyl-1-(oxan-2-ylmethyl)pyrazol-5-yl]-N,N-dimethylmethanimidamide

HRID 717249

Reaction equation

HRID 717249 reaction equation
[C:1]([C:5]1[CH:9]=[C:8](/[N:10]=[CH:11]/[N:12]([CH3:14])[CH3:13])[NH:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:18][CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][O:20]1.[I-].[Na+]>CN(C)C=O>[C:1]([C:5]1[CH:9]=[C:8](/[N:10]=[CH:11]/[N:12]([CH3:14])[CH3:13])[N:7]([CH2:18][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][O:20]2)[N:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 24758Sodium hydrideHCID 1419172-(Bromomethyl)tetrahydro-2H-pyranHCID 178484244HCID 178484244, compound

Product 1

HCID 87440113N'-[3-tert-butyl-1-(oxan-2-ylmethyl)pyrazol-5-yl]-N,N-dimethylmethanimidamideYield 55%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of Example 63A (1.0 g, 5.2 mmol) in N,N-dimethylformamide (10 mL) were added sodium hydride (0.52 g, 12.9 mmol, 60% in mineral oil, Aldrich), 2-(bromomethyl)tetrahydro-2H-pyran (0.8 mL, 6.2 mmol) and sodium iodide (0.23 g, 1.5 mmol). After stirring at 65° C. for 16 h, the reaction mixture was cooled and quenched with saturated NaHCO3 (10 mL). The aqueous layer was extracted with ethyl acetate (3×20 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography using an Analogix® Intelliflash280™ (SiO2, 0-10% methanol in dichloromethane) to provide 0.82 g (55%) of the title compound. 1H NMR (501 MHz, chloroform-d) δ ppm 1.22-1.33 (m, 1H), 1.27 (s, 9H), 1.34-1.49 (m, 3H), 1.51-1.62 (m, 1H), 1.72-1.83 (m, 1H), 2.87 (s, 3H), 2.95 (s, 3H), 3.36-3.49 (m, 1H), 3.73-3.83 (m, 1H), 3.95 (dd, J=11.3, 3.0 Hz, 1H), 4.02 (dd, J=13.4, 7.7 Hz, 1H), 4.17 (dd, J=13.4, 5.8 Hz, 1H), 5.55 (s, 1H), 8.00 (s, 1H). MS (ESI+) m/z 293 (M+H)+.

Workup

  1. temperaturethe reaction mixture was cooled
  2. customquenched with saturated NaHCO3 (10 mL)
  3. extractionThe aqueous layer was extracted with ethyl acetate (3×20 mL)
  4. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-573ca114e50e4708a4650b867a3a89da
Source dataset
uspto-grants-2015_11
Patent number
US09193713B2

Linked notes

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