Dichloromethane → 1-Cyclopentyl-3-ethyl-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one

HRID 2268144Notes

Reaction equation

HRID 2268144 reaction equation
[CH:1]1([N:6]2[C:10]3[C:11](=[O:24])[N:12](CC4C=CC(OC)=CC=4)[CH2:13][CH2:14][C:9]=3[C:8]([CH2:25][CH3:26])=[N:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.FC(F)(F)C(O)=O.CS(O)(=O)=O.C(Cl)Cl>O>[CH:1]1([N:6]2[C:10]3[C:11](=[O:24])[NH:12][CH2:13][CH2:14][C:9]=3[C:8]([CH2:25][CH3:26])=[N:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 6395Methanesulfonic AcidHCID 6422Trifluoroacetic acidHCID 98064151-Cyclopentyl-3-ethyl-6-[(4-methoxyphenyl)methyl]-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one

Product 1

HCID 108235421-Cyclopentyl-3-ethyl-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

The reaction mixture from Example 8 was cooled to 55° C. and slowly thereto trifluoroacetic acid (87.3 kg, 764 moles) was added while keeping the temperature between 50-60° C. The first ⅓ of the charge was exothermic and required external cooling. Methanesulfonic acid (6342 ml, 97.7 moles) was added and the reaction was warmed to ˜70° C. for two hours. The reaction was cooled to 20-25° C. and methylene chloride (17 gal, 64 L) was added followed by the slow addition of water (17 gal, 64 L). The layers were separated and the aqueous layer was diluted further with water (6 gal, 22.7 L) and then re-extracted with methylene chloride (6 gal, 22.7 L). The combined methylene chloride layers were mixed with water (29 gal, 110 L) and then brought to pH˜7.0 by the addition of saturated sodium bicarbonate (ca. 45 gal, 170 L). The layers were separated and the methylene chloride atmospherically distilled to about 9 gal (35 L). Ethyl acetate (13 gal, 49 L) was added and the reaction mixture was distilled to about 9 gal (35 L). The resulting slurry was cooled and granulated. The solids were collected by filtration, washed with ethyl acetate and vacuum dried at 40° C. under full vacuum. The yield was 7.91 kg, 71.2%; mp 152-153° C.

Workup

  1. custombetween 50-60° C
  2. temperatureThe reaction was cooled to 20-25° C.
  3. customThe layers were separated
  4. additionthe aqueous layer was diluted further with water (6 gal, 22.7 L)
  5. extractionre-extracted with methylene chloride (6 gal, 22.7 L)
  6. additionThe combined methylene chloride layers were mixed with water (29 gal, 110 L)
  7. additionbrought to pH˜7.0 by the addition of saturated sodium bicarbonate (ca. 45 gal, 170 L)
  8. customThe layers were separated
  9. distillationthe methylene chloride atmospherically distilled to about 9 gal (35 L)
  10. additionEthyl acetate (13 gal, 49 L) was added
  11. distillationthe reaction mixture was distilled to about 9 gal (35 L)
  12. temperatureThe resulting slurry was cooled
  13. filtrationThe solids were collected by filtration
  14. washwashed with ethyl acetate and vacuum
  15. customdried at 40° C. under full vacuum

Sources & evidence

ORD record
ord-f250e9a5cd8741cbbb5e1620b869b791
Source dataset
uspto-grants-2001_12
Patent number
US06326495B2

Reaction notes

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