3,4-dihydro-2H-pyran → HCID 86664601, compound

HRID 921529Notes

Reaction equation

HRID 921529 reaction equation
[O:1]1[CH:6]=[CH:5][CH2:4][CH2:3][CH2:2]1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.[Cl:22][C:23]1[C:28]2[C:29]([CH:32]([CH3:34])[CH3:33])=[N:30][NH:31][C:27]=2[CH:26]=[CH:25][N:24]=1>C(OCC)(=O)C>[Cl:22][C:23]1[C:28]2[C:29]([CH:32]([CH3:34])[CH3:33])=[N:30][N:31]([CH:6]3[CH2:5][CH2:4][CH2:3][CH2:2][O:1]3)[C:27]=2[CH:26]=[CH:25][N:24]=1

Participants

5

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 178440414HCID 178440414, compound

Product 1

HCID 86664601HCID 86664601, compoundYield 93%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Dihydropyran (10.0 mL) and (+)-10-camphorsulfonic acid (0.062 g) were sequentially added to compound (4a) (0.55 g), followed by stirring at 80° C. for 30 min. After cooling, the reaction solution was distributed between ethyl acetate and a saturated aqueous sodium bicarbonate solution, and the organic layer was washed with saturated saline. The organic layer after the washing was dried over anhydrous sodium sulfate, and the solvent was distilled away. The residue was purified by neutral silica gel column chromatography (n-hexane/ethyl acetate) to obtain 4-chloro-3-isopropyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[4,3-c]pyridine (0.727 g, 93%) as a colorless oily substance. Subsequently, tetrakis(triphenylphosphine)palladium(0) (0.149 g) was added to a solution of the colorless oily substance (0.727 g), quinoline-3-boronic acid (0.539 g), and an aqueous sodium carbonate solution (1 M, 13 mL) in ethylene glycol dimethyl ether (26 mL) under a nitrogen atmosphere at 85° C. for 25 hr. The reaction solution was distributed between ethyl acetate and water, and the organic layer was washed with saturated saline and then dried over anhydrous sodium sulfate. After distillation of the solvent, THF (5.2 mL) and concentrated hydrochloric acid (2.6 mL) were added to the residue, followed by stirring at 60° C. for 1 hr. The pH was adjusted to 7 with an aqueous sodium bicarbonate solution, followed by extraction with ethyl acetate. The organic layer was washed with saturated saline. The organic layer after the washing was dried over anhydrous sodium sulfate, and then the solvent was distilled away. The residue was purified by neutral silica gel column chromatography (n-hexane/ethyl acetate) to obtain compound (4b) (0.395 g, the third yield: 52%) as a white solid.

Workup

  1. temperatureAfter cooling
  2. washa saturated aqueous sodium bicarbonate solution, and the organic layer was washed with saturated saline
  3. dry with materialThe organic layer after the washing was dried over anhydrous sodium sulfate
  4. distillationthe solvent was distilled away
  5. customThe residue was purified by neutral silica gel column chromatography (n-hexane/ethyl acetate)

Sources & evidence

ORD record
ord-727831ed50e74abfb85b1d37f834e208
Source dataset
uspto-grants-2016_03
Patent number
US09273045B2

Reaction notes

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