Hydrochloric Acid → HCID 44515369, compound

HRID 452864Notes

Reaction equation

HRID 452864 reaction equation
F[C:2](F)(F)[C:3]([OH:5])=[O:4].[C:8]1([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH:13]=[CH:12][C:11]([N:14]2[C:18]3=[N:19][CH:20]=C(C#N)[CH:22]=[C:17]3[C:16]3([CH2:29][CH2:28][N:27]([CH2:30][C:31]4[C:36]([CH3:37])=[CH:35][CH:34]=[CH:33][N:32]=4)[CH2:26][CH2:25]3)[C:15]2=[O:38])=[CH:10][CH:9]=1.S(=O)(=O)(O)O.[OH-].[Li+].Cl>O.C1COCC1.C(O)C>[C:8]1([C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=2)[CH:9]=[CH:10][C:11]([N:14]2[C:18]3=[N:19][CH:20]=[C:2]([C:3]([OH:5])=[O:4])[CH:22]=[C:17]3[C:16]3([CH2:29][CH2:28][N:27]([CH2:30][C:31]4[C:36]([CH3:37])=[CH:35][CH:34]=[CH:33][N:32]=4)[CH2:26][CH2:25]3)[C:15]2=[O:38])=[CH:12][CH:13]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 1118Sulfuric AcidHCID 3939Lithium HydroxideHCID 6422Trifluoroacetic acidHCID 44515072HCID 44515072, compound

Product 1

HCID 44515369HCID 44515369, compound

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

The title compound of Example 4, 1′-biphenyl-4-yl-1-[(3-methylpyridin-2-yl)methyl]-2′-oxo-1′,2′-dihydrospiro[piperidine-4,3′-pyrrolo[2,3-b]pyridine]-5′-carbonitrile, (1 mmol) was combined with anhydrous ethanol (10 mL) and neat sulfuric acid (1 mL) was added drop wise to the solution over 2 minutes. The resulting mixture is heated in a sealed tube to 100° C., allowed to cool to room temperature and combined with ice water. The resulting mixture was extracted with methylene chloride, dried and concentrated. The crude oil is combined with THF (10 mL), water (5 mL) and lithium hydroxide (20 mmol) and heated to 50° C. for 5 h, acidified with 1 m HCl, concentrated and purified by preparative reverse phase HPLC (method C), which provided the title compound, isolated as a salt of trifluoroacetic acid.

Workup

  1. additionwas added drop wise to the solution over 2 minutes
  2. temperatureto cool to room temperature
  3. extractionThe resulting mixture was extracted with methylene chloride
  4. customdried
  5. concentrationconcentrated
  6. temperatureheated to 50° C. for 5 h
  7. concentrationconcentrated
  8. custompurified by preparative reverse phase HPLC (method C), which

Sources & evidence

ORD record
ord-4e8d83727b564344b065fe9ccc2574bc
Source dataset
uspto-grants-2013_07
Patent number
US08492398B2

Reaction notes

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