1-Methylpiperazine → HCID 54219936, compound

HRID 655043Notes

Reaction equation

HRID 655043 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[NH:9][N:10]=[C:11](Cl)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[F:18].[CH3:20][N:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1>O1CCCC1>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[NH:9][N:10]=[C:11]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[F:18])[N:24]1[CH2:25][CH2:26][N:21]([CH3:20])[CH2:22][CH2:23]1

Participants

4

Reactant 2

HCID 531671-MethylpiperazineHCID 72745344HCID 72745344, compound

Product 1

HCID 54219936HCID 54219936, compoundYield 118.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred mixture of α-chloro-2-fluorobenzaldehyde 2,4-dichlorophenylhydrazone (51.0 g, 0.16 mol) and tetrahydrofuran (500 ml) under N2 was added dropwise, 1-methylpiperazine (35.4 g, 0.35 mol). The reaction was allowed to stir for 16 hours and then was cooled in an ice bath for 30 minutes. The mixture was filtered and washed with cold tetrahydrofuran leaving behind the insoluble 1-methylpiperazine hydrochloride. The filtrate was concentrated to afford 72.5 g of 1-{[(2,4-dichlorophenyl) hydrazono](2-fluorophenyl)methyl}-4-methylpiperazine as an oil. To a stirred mixture of the oil (72.5 g, 0.19 mol) and tetrahydrofuran (200 ml), under N2, was added dropwise, potassium tert-butoxide (23.5 g, 0.21 mol) dissolved in tetrahydrofuran (400 ml). The reaction was allowed to stir at ambient temperature for 58 hours. The reaction mixture was concentrated to an oily residue, which was partitioned between ether and H2O. The ether extract was washed with H2O, dried with MgSO4 and concentrated to 58.0 g of an oil. A 9.0 g sample of the oil was flash chromatographed over 500 g silica gel eluting with 20% methanol-CH2Cl2. Concentration of appropriate fractions afforded 5.7 g (55%) of an oil. The oil was dissolved in anhydrous ether and fumaric acid (2.0 g, 1.1 eq) was added. The mixture was stirred overnight and the solid was collected by filtration to afford 4.6 g of product. A 3.8 g sample was recrystallized twice from ethyl acetate to afford 2.2 g of 1-(2,4-dichlorophenyl)-3-(4-methyl-1-piperazinyl)-1H-indazole, m.p. 150°-152° C.

Workup

  1. additionwas added dropwise
  2. temperaturewas cooled in an ice bath for 30 minutes
  3. filtrationThe mixture was filtered
  4. washwashed with cold tetrahydrofuran leaving behind the insoluble 1-methylpiperazine hydrochloride
  5. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-b08ceebcef7d4507a08cde7177d02c1b
Source dataset
uspto-grants-1992_07
Patent number
US05134236

Reaction notes

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