4-[1-(Phenylsulfonyl)-1H-indazol-3-yl]-1-piperazinecarbonitrile → 3-(Piperazin-1-YL)-1H-indazole

HRID 1955840Notes

Reaction equation

HRID 1955840 reaction equation
C1(S([N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]([N:19]3[CH2:24][CH2:23][N:22](C#N)[CH2:21][CH2:20]3)=[N:11]2)(=O)=O)C=CC=CC=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[N:19]1([C:12]2[C:13]3[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=3)[NH:10][N:11]=2)[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1

Participants

4

Reactant 2

HCID 148234434-[1-(Phenylsulfonyl)-1H-indazol-3-yl]-1-piperazinecarbonitrileHCID 21226445Aluminium lithium hydride2×

Product 1

HCID 148234453-(Piperazin-1-YL)-1H-indazoleYield 418%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred mixture of 4-[1-(phenylsulfonyl)-1H-indazol-3-yl]-1-piperazine-carbonitrile (163 g, 0.44 mol) in tetrahydrofuran (2.01) was added, dropwise, lithium aluminum hydride (880 ml; 0.88 mol of a 1M lithium aluminum hydride solution in tetrahydrofuran). After complete addition, the reaction was heated to reflux and stirred for 6 hours, stirred at ambient temperature for one hour and allowed to sit at room temperature overnight. The reaction was quenched by the careful dropwise addition of water. After no more hydrogen could be observed to evolve, the reaction was filtered and the lithium salt filter cake was washed well with tetrahydrofuran. The filtrate was combined with the filtrate of another run (all together the starting material totaled 300 g, i.e. 820 mmol) and the combined filtrates were concentrated to afford 372 g of a yellow solid suspended in water. An attempt was made to partition the product between water and dichloromethane, but the product proved to be only slightly soluble in dichloromethane. Therefore, the biphasic product suspension was filtered through a course sintered funnel and the white product which was collected was dried to afford 121 g. The two phases of the filtrate were separated and the water was extracted again with dichloromethane. All of the dichloromethane phases were combined, washed twice with water, dried with magnesium sulfate, and concentrated to afford 41 g of a brown residue. The residue was triturated with diethyl ether and filtered to afford 10 g of a beige solid, m.p.=139°-150° C. The NMR and MS spectra were consistent with the structure. Recrystallization of 10 g from toluene afforded 7.5 g of 3-(1-piperazinyl-1H-indazole, m.p. 153°≥155° C.

Workup

  1. additionwas added
  2. additionAfter complete addition
  3. temperaturethe reaction was heated
  4. temperatureto reflux
  5. stirringstirred at ambient temperature for one hour
  6. waitto sit at room temperature overnight
  7. customThe reaction was quenched by the careful dropwise addition of water
  8. filtrationthe reaction was filtered
  9. filtrationthe lithium salt filter cake
  10. washwas washed well with tetrahydrofuran
  11. concentrationwere concentrated

Sources & evidence

ORD record
ord-e89b27ef163c4c9788603999f36a4c37
Source dataset
uspto-grants-1998_07
Patent number
US05776963

Reaction notes

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