Hydrochloric Acid → Ammonia methanol dichloromethane

HRID 558274Notes

Reaction equation

HRID 558274 reaction equation
B.[Cl:2][C:3]1[CH:4]=[C:5]([CH:19]=[C:20]([Cl:22])[CH:21]=1)[O:6][C:7]1[C:8]([CH2:17][CH3:18])=[N:9][N:10]2[CH2:15][CH2:14][NH:13][C:12](=O)[C:11]=12.[ClH:23]>O1CCCC1>[Cl:23][CH2:20][Cl:22].[CH3:5][OH:6].[NH3:9].[Cl:22][C:20]1[CH:19]=[C:5]([CH:4]=[C:3]([Cl:2])[CH:21]=1)[O:6][C:7]1[C:8]([CH2:17][CH3:18])=[N:9][N:10]2[CH2:15][CH2:14][NH:13][CH2:12][C:11]=12

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 6331Borane4×HCID 21949864HCID 21949864, compound

Product 2

HCID 21584172Ammonia methanol dichloromethaneHCID 21949827HCID 21949827, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent5×

Procedure

Borane (2.00 ml of a 1.0M solution in tetrahydrofuran, 2.00 mmol) was added to a stirred solution of the pyrazole of Example 97 (326 mg, 1.00 mmol) in tetrahydrofuran (10 ml) at room temperature under nitrogen. The reaction was heated under reflux for 5 hours and further borane (3.00 ml of a 1.0M solution in tetrahydrofuran, 3.00 mmol) was added. The reaction was heated under reflux for 14 hours and further borane (2.00 ml of a 1.0M solution in tetrahydrofuran, 2.00 mmol) was added. The reaction was heated under reflux for 3 hours and further borane (2.00 ml of a 1.0M solution in tetrahydrofuran, 2.00 mmol) was added. The mixture was cooled to room temperature, 2M hydrochloric acid (10 ml) was added and the mixture was heated under reflux for 1 hour, The mixture was cooled to room temperature and concentrated under reduced pressure. The residue was dissolved in dichloromethane (40 ml), washed with 1M aqueous potassium carbonate solution (30 ml), dried over magnesium sulphate, filtered and concentrated under reduced pressure. The crude product was purified by flash column chromatography on silica gel eluting with dichloromethane:methanol (98:2, by volume), then dichloromethane:methanol (95:5, by volume) and then dichloromethane:methanol:ammonia (90:9:1, by volume) to provide the title compound (219 mg) as a white solid, m.p. 76-77° C.

Workup

  1. temperatureThe reaction was heated
  2. temperatureunder reflux for 5 hours
  3. temperatureThe reaction was heated
  4. temperatureunder reflux for 14 hours
  5. temperatureThe reaction was heated
  6. temperatureunder reflux for 3 hours
  7. temperaturethe mixture was heated
  8. temperatureunder reflux for 1 hour
  9. temperatureThe mixture was cooled to room temperature
  10. concentrationconcentrated under reduced pressure
  11. dissolutionThe residue was dissolved in dichloromethane (40 ml)
  12. washwashed with 1M aqueous potassium carbonate solution (30 ml)
  13. dry with materialdried over magnesium sulphate
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure
  16. customThe crude product was purified by flash column chromatography on silica gel eluting with dichloromethane:methanol (98:2, by volume)

Sources & evidence

ORD record
ord-e972a3e493874fa8bc07cc34933fc54e
Source dataset
uspto-grants-2011_11
Patent number
US08063044B2

Reaction notes

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