Ethyl Acetate → 4-chloro-1-(2-cyclopropyl-3-methyl-2H-indazol-5-yl)pyridin-2(1H)-one

HRID 1497408Notes

Reaction equation

HRID 1497408 reaction equation
[CH:1]1([N:4]2[C:12]([CH3:13])=[C:11]3[C:6]([CH:7]=[CH:8][C:9]([N:14]4[CH:19]=[CH:18][C:17](O)=[CH:16][C:15]4=[O:21])=[CH:10]3)=[N:5]2)[CH2:3][CH2:2]1.P(Cl)(Cl)([Cl:24])=O.C(OCC)(=O)C>CN(C=O)C>[Cl:24][C:17]1[CH:18]=[CH:19][N:14]([C:9]2[CH:8]=[CH:7][C:6]3[C:11](=[C:12]([CH3:13])[N:4]([CH:1]4[CH2:3][CH2:2]4)[N:5]=3)[CH:10]=2)[C:15](=[O:21])[CH:16]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 24813Phosphorus oxychlorideHCID 1177986831-(2-cyclopropyl-3-methyl-2H-indazol-5-yl)-4-hydroxypyridin-2(1H)-one

Product 1

HCID 1177986084-chloro-1-(2-cyclopropyl-3-methyl-2H-indazol-5-yl)pyridin-2(1H)-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
45 °C

Procedure

To a suspension of 1-(2-cyclopropyl-3-methyl-2H-indazol-5-yl)-4-hydroxypyridin-2(1H)-one (118 g) in DMF (2 L) was added phosphorus oxychloride (46.9 ml) at room temperature, and the mixture was stirred under an argon atmosphere at an inside temperature of 45° C. for 22 hr. The reaction mixture was poured into ethyl acetate (3 L), and washed with saturated aqueous sodium hydrogen carbonate (1.5 L). The obtained aqueous layer was extracted twice with ethyl acetate (2 L and 1 L). The organic layer was washed with aqueous sodium sulfite solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was dissolved in a 1:1 mixed solvent (1.1 L) of ethyl acetate and tetrahydrofuran with heating, and the mixture was filtered through NH silica gel (750 g). The eluate was concentrated under reduced pressure, and the obtained residue was solidified with diisopropyl ether to give the title compound (73.2 g).

Workup

  1. washwashed with saturated aqueous sodium hydrogen carbonate (1.5 L)
  2. extractionThe obtained aqueous layer was extracted twice with ethyl acetate (2 L and 1 L)
  3. washThe organic layer was washed with aqueous sodium sulfite solution and saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe residue was dissolved in a 1:1 mixed solvent (1.1 L) of ethyl acetate and tetrahydrofuran
  7. temperaturewith heating
  8. filtrationthe mixture was filtered through NH silica gel (750 g)
  9. concentrationThe eluate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-a2b713791d9c4d0fbf4de829be700f1c
Source dataset
uspto-grants-2015_12
Patent number
US09199963B2

Reaction notes

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