Dimethylformamide → 3-[4-(cyclopropyl)methyl-1-piperazinyl]-1-(4-fluorophenyl)-1H-indazole

HRID 359019Notes

Reaction equation

HRID 359019 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]([N:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)=[N:9]2)=[CH:4][CH:3]=1.C(=O)(O)[O-].[Na+].Cl[CH2:29][CH:30]1[CH2:32][CH2:31]1.CN(C)C=O>O>[CH:30]1([CH2:29][N:20]2[CH2:19][CH2:18][N:17]([C:10]3[C:11]4[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=4)[N:8]([C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=4)[N:9]=3)[CH2:22][CH2:21]2)[CH2:32][CH2:31]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 80013(Chloromethyl)cyclopropane2×HCID 516892Sodium BicarbonateHCID 151170821-(4-fluorophenyl)-3-(1-piperazinyl)-1H-indazole

Product 1

HCID 151170863-[4-(cyclopropyl)methyl-1-piperazinyl]-1-(4-fluorophenyl)-1H-indazole

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A stirred mixture of 5.0 g of 1-(4-fluorophenyl)-3-(1-piperazinyl)-1H-indazole, 1.6 g of sodium bicarbonate, 1.7 g of chloromethylcyclopropane and 60 ml of dimethylformamide was heated at 85°-90° for 16 hours. Additional chloromethylcyclopropane (0.43 g) was added and the reaction mixture heated at 85°-90° for 8 hrs. The reaction mixture was then poured into water and the aqueous mixture extracted with ethyl acetate. The extract was washed with water, dried over anhydrous magnesium sulfate and concentrated to a solid. The solid was purified by flash chromatography on silica gel utilizing ethyl acetate/diethylamine (3%) as the eluent. Concentration of the appropriate fractions gave 3-[4-(cyclopropyl)methyl-1-piperazinyl]-1-(4-fluorophenyl)-1H-indazole as a solid. The solid was dissolved in anhydrous diethyl ether and treated with ethereal hydrogen chloride to give the hydrochloride salt. The salt was recrystallized from ethanol-diethyl ether (twice) to give 2.6 g (40%) of 3-[4-(cyclopropyl)methyl-1-piperazinyl] -1-(4-fluorophenyl)-1H-indazole hydrochloride, mp 213°-215°.

Workup

  1. temperaturewas heated at 85°-90° for 16 hours
  2. temperaturethe reaction mixture heated at 85°-90° for 8 hrs
  3. extractionthe aqueous mixture extracted with ethyl acetate
  4. washThe extract was washed with water
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated to a solid
  7. customThe solid was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-5c9f96a46ed34a2f8409b3d92e49eb3f
Source dataset
uspto-grants-1991_03
Patent number
US04999356

Reaction notes

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