Sulfuric Acid → HCID 23048179, compound

HRID 1382595Notes

Reaction equation

HRID 1382595 reaction equation
[F:1][C:2]([F:27])([F:26])[C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]([CH:18]3[CH2:23][CH2:22][N:21](C#N)[CH2:20][CH2:19]3)=[N:10]2)=[CH:5][CH:4]=1.OS(O)(=O)=O.[OH-].[Na+]>O>[F:27][C:2]([F:1])([F:26])[C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]([CH:18]3[CH2:19][CH2:20][NH:21][CH2:22][CH2:23]3)=[N:10]2)=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 14032656HCID 14032656, compound

Product 1

HCID 23048179HCID 23048179, compoundYield 93%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A stirred mixture of 4-[1-(4-(trifluoromethyl)phenyl)-1H-indazol-3-yl]piperidine-1-carbonitrile of Example 101 (15 g, 0.041 moles) and 25% H2SO4 (100 ml) was refluxed for 20 hours. The mixture was cooled. poured into H2O and basified with a 25% NaOH solution. The product was extracted (dichloromethane), dried (MgSO4), and concentrated to yield 13 g (93%) of 1-[4-(trifluoromethyl)phenyl]-3-(4-piperidinyl)-1H-indazole as an oil. To a stirred suspension of the indazole (4.0 g, 0.012 moles) in toluene (60 ml) was added methyl isocyanate (0.75 ml., 0.013 moles). The temperature of the reaction mixture rose to 35° C. following the addition. The mixture was stirred for 2 hours at ambient temperature and then concentrated to yield 4.6 g of a solid. The product was purified by high pressure liquid chromatography (3.5% methanol-CHCl3 ; silica gel) and then recrystallized three times from toluene-hexane to yield 2.93 g (63%) of N-methyl-4-[1-(4-trifluoromethyl)phenyl]-1H-indazol-3-yl]piperidine-1-carboxamide, m.p.: 150°-152° C.

Workup

  1. temperaturewas refluxed for 20 hours
  2. temperatureThe mixture was cooled
  3. extractionThe product was extracted (dichloromethane)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-d8afe56060724b7b817f45ec94d2d980
Source dataset
uspto-grants-1989_02
Patent number
US04806649

Reaction notes

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