Hydrochloric Acid → HCID 178428953, compound

HRID 1486333Notes

Reaction equation

HRID 1486333 reaction equation
[F:1][C:2]1[CH:34]=[CH:33][CH:32]=[C:31]([F:35])[C:3]=1[CH2:4][O:5][C:6]1[N:11]2[N:12]=[C:13]([CH3:29])[C:14]([C:15]([NH:17][CH2:18][C@H:19]3[CH2:24][CH2:23][C@H:22]([C:25]([O:27]C)=[O:26])[CH2:21][CH2:20]3)=[O:16])=[C:10]2[CH:9]=[C:8]([CH3:30])[CH:7]=1.[OH-].[Li+].Cl>C1COCC1.CO>[F:1][C:2]1[CH:34]=[CH:33][CH:32]=[C:31]([F:35])[C:3]=1[CH2:4][O:5][C:6]1[N:11]2[N:12]=[C:13]([CH3:29])[C:14]([C:15]([NH:17][CH2:18][C@H:19]3[CH2:20][CH2:21][C@H:22]([C:25]([OH:27])=[O:26])[CH2:23][CH2:24]3)=[O:16])=[C:10]2[CH:9]=[C:8]([CH3:30])[CH:7]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium Hydroxide2×HCID 178501127HCID 178501127, compound

Product 1

HCID 178428953HCID 178428953, compoundYield 51.3%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

90 mg (0.19 mmol, 1.0 eq.) of methyl trans-4-{[({7-[(2,6-difluorobenzyl)oxy]-2,5-dimethylpyrazolo[1,5-a]pyridin-3-yl}carbonyl)amino]methyl}cyclohexanecarboxylate from Example 35 were dissolved in 5.5 ml of THF/methanol (5/1) and admixed with 1.3 ml of 1 N aqueous lithium hydroxide solution. The mixture was stirred at RT for 3 days. Subsequently, another 2 ml of 1 N lithium hydroxide solution were added and the mixture was stirred at 60° C. for 7 days. After cooling, the mixture was acidified to pH=3 with 1 N hydrochloric acid and freed of the organic solvents on a rotary evaporator. The resulting aqueous phase was extracted three times with dichloromethane and the combined organic phases were washed with water, then dried with sodium sulphate, filtered and concentrated. The residue was purified by means of thick-layer chromatography (eluent:dichloromethane/methanol=20/1). 46 mg of the target compound were obtained (53% of theory).

Workup

  1. stirringthe mixture was stirred at 60° C. for 7 days
  2. temperatureAfter cooling
  3. customfreed of the organic solvents on a rotary evaporator
  4. extractionThe resulting aqueous phase was extracted three times with dichloromethane
  5. washthe combined organic phases were washed with water
  6. dry with materialdried with sodium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by means of thick-layer chromatography (eluent:dichloromethane/methanol=20/1)

Sources & evidence

ORD record
ord-26bff7156c754813a35ccc32f4982d1a
Source dataset
uspto-grants-2016_08
Patent number
US09422285B2

Reaction notes

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