Hydrochloric Acid → HCID 86661971, compound

HRID 1259350Notes

Reaction equation

HRID 1259350 reaction equation
[CH3:1][C:2]1[N:3](C(OCC)=O)[C:4](=O)[CH:5]=[C:6]2[CH2:10][N:9]([C:11]3[CH:12]=[N:13][N:14]([CH2:16][C:17]([F:20])([F:19])[F:18])[CH:15]=3)[C:8](=[O:21])[C:7]=12.Cl.P(Cl)(Cl)([Cl:31])=O>C1COCC1>[Cl:31][C:4]1[N:3]=[C:2]([CH3:1])[C:7]2[C:8](=[O:21])[N:9]([C:11]3[CH:12]=[N:13][N:14]([CH2:16][C:17]([F:20])([F:19])[F:18])[CH:15]=3)[CH2:10][C:6]=2[CH:5]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 24813Phosphorus oxychlorideHCID 66742838HCID 66742838, compound

Product 1

HCID 86661971HCID 86661971, compoundYield 68.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
95 °C

Procedure

As shown in step 21-iv of Scheme 21, to a solution of Compound 2066 (614 mg, 1.58 mmol) in THF (10 mL) was added HCl (6 M, 10 mL) at rt. The reaction mixture was heated at reflux overnight and then concentrated under reduced pressure. To the residue was added phosphorus oxychloride (15 mL, 161 mmol) and the reaction mixture was heated at 95° C. for 3 hours under an atmosphere of nitrogen. After cooling and concentrating the mixture under reduced pressure, ice was added followed by the addition of EtOAc 30 minutes later. The aqueous layer was extracted with EtOAc and the combined organics washed with brine, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by silica gel chromatography (petroleum ether:EtOAc, 1:1) gave 6-chloro-4-methyl-2-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one (Compound 2067, 356 mg, 68%) as a white solid: ESMS (M+H) 330.90.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux overnight
  3. concentrationconcentrated under reduced pressure
  4. temperatureAfter cooling
  5. concentrationconcentrating the mixture under reduced pressure, ice
  6. additionwas added
  7. additionfollowed by the addition of EtOAc 30 minutes later
  8. extractionThe aqueous layer was extracted with EtOAc
  9. washthe combined organics washed with brine
  10. dry with materialdried (sodium sulfate)
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customPurification by silica gel chromatography (petroleum ether:EtOAc, 1:1)

Sources & evidence

ORD record
ord-3910516732334b93819a286810fc6343
Source dataset
uspto-grants-2013_06
Patent number
US08466288B2

Reaction notes

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