Hydrochloric Acid → HCID 136343645, compound

HRID 1594392Notes

Reaction equation

HRID 1594392 reaction equation
[ClH:1].[CH:2]1([C:6]2[NH:7][N:8]=[C:9]3[C:14]=2[C:13]([CH3:15])=[CH:12][C:11](=[O:16])[NH:10]3)[CH2:5][CH2:4][CH2:3]1.Cl>CO.[Pd]>[ClH:1].[CH:2]1([C:6]2[NH:7][N:8]=[C:9]3[C:14]=2[CH:13]([CH3:15])[CH2:12][C:11](=[O:16])[NH:10]3)[CH2:3][CH2:4][CH2:5]1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 136140500HCID 136140500, compound

Product 1

HCID 136343645HCID 136343645, compoundYield 11%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst2×HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

To an aliquot of 3-cyclobutyl-4-methyl-2,7-dihydro-pyrazolo[3,4-b]pyridin-6-one hydrochloride salt (0.20 mg, 0.83 mmol) in MeOH (50 mL) was added 10% Pd/C (100 mg). The reaction mixture was placed in a hydrogenation bottle, pressured with 45 psi H2, and then heated to 60° C. (internal temp). After 12 hr, the reaction was cooled to room temperature, 100 μL of conc. HCl was added, followed by an additional 100 mg of Pd/C. The bottle was re-pressurized with 45 psi H2, and then reheated to 60° C. (internal temp). The reaction mixture was cooled to room temperature after 12 hr, filtered through a plug of diatomaceous earth, and concentrated under pressure. Partial purification of this material was accomplished by MPLC using a 15 g ISCO column (ISCO, Inc., Lincoln, Nebr.), eluting with 2% MeOH/CH2Cl2 with 0.2% NH4OH. The product-containing fractions were collected and concentrated. This material was re-chromatographed using a 15 g ISCO column, eluting with 4% MeOH/CH2Cl2 with 0.2% NH4OH. The product-containing fractions were collected and concentrated to afford the title compound (19.0 mg, 11% yield). The monohydrochloride salt was formed using 1M HCl in Et2O. 400 MHz 1H NMR (CD3OD) free base d 3.60 (dddd, J=9.5,9.5, 9.5, 0.8 Hz, 1H), 3.10 (ddddd, J=10.8, 6.6, 6.6, 6.6, 4.2 Hz, 1H), 2.72 (dd, J=15.8, 6.6 Hz, 1H), 2.36-2.23 (M, 5H), 2.07 (dddd, J=19.9, 9.5, 9.5, 9.5 Hz, 1H), 1.94-1.89 (m, 1H), 1.15 (d, J=7.0 Hz, 3H). LRMS m/z (APCI+) 206 (M+1).

Workup

  1. temperaturethe reaction was cooled to room temperature
  2. customreheated to 60° C.
  3. temperatureThe reaction mixture was cooled to room temperature after 12 hr
  4. filtrationfiltered through a plug of diatomaceous earth
  5. concentrationconcentrated under pressure
  6. customPartial purification of this material
  7. washeluting with 2% MeOH/CH2Cl2 with 0.2% NH4OH
  8. customThe product-containing fractions were collected
  9. concentrationconcentrated
  10. customThis material was re-chromatographed
  11. washeluting with 4% MeOH/CH2Cl2 with 0.2% NH4OH
  12. customThe product-containing fractions were collected
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-c53656bb93464ff08e0bcfc1129331c7
Source dataset
uspto-grants-2007_11
Patent number
US07300944B2

Reaction notes

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