HCID 15020539, compound → HCID 14823467, compound

HRID 1031520Notes

Reaction equation

HRID 1031520 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[C:5]2[N:11]1[CH2:16][CH2:15][N:14](C#N)[CH2:13][CH2:12]1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[C:5]2[N:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1

Participants

4

Reactant 2

HCID 15020539HCID 15020539, compoundHCID 21226445Aluminium lithium hydride2×

Product 1

HCID 14823467HCID 14823467, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of 4-(5-chloro-1H-indazol-3-yl)-1-piperazinecarbonitrile of Example 36a in THF (175 ml) under N2 was added, dropwise, lithium aluminum hydride (20 ml, 0.02 mol of a 1M lithium aluminum hydride solution in THF). After total addition, the reaction was heated to reflux and stirred for 3 hours. The reaction was cooled in an ice bath and the excess lithium aluminum hydride was destroyed by the dropwise addition of H2O (15 ml). This was filtered through a coarse sintered glass funnel and the filter cake was washed well with THF. The filtrate was concentrated to afford a biphasic H2O-oil (7.5 g). This was partitioned between CH2Cl2 and H2O and the H2O was extracted again with CH2Cl2 adding a small amount of saturated NaCl solution. The combined CH2Cl2 extract was washed with H2O, dried with MgSO4 and concentrated to afford 3.2 g of a solid, m.p. 60°-62° C. The solid was purified by preparative HPLC (Water's Associates Prep. LC/System 500, 2 silica gel columns eluting with 20% methanol-CH2Cl2) to afford 1.9 g of product. A small amount was recrystallized from toluene and collected, then washed with hexane affording solid 5-chloro-3-(1-piperazinyl)-1H-indazole, m.p. 178°-180° C.

Workup

  1. additionAfter total addition
  2. temperaturethe reaction was heated
  3. temperatureto reflux
  4. temperatureThe reaction was cooled in an ice bath
  5. customthe excess lithium aluminum hydride was destroyed by the dropwise addition of H2O (15 ml)
  6. filtrationThis was filtered through a coarse sintered glass funnel
  7. washthe filter cake was washed well with THF
  8. concentrationThe filtrate was concentrated
  9. customto afford a biphasic H2O-oil (7.5 g)
  10. customThis was partitioned between CH2Cl2 and H2O
  11. extractionthe H2O was extracted again with CH2Cl2 adding a small amount of saturated NaCl solution
  12. extractionThe combined CH2Cl2 extract
  13. washwas washed with H2O
  14. dry with materialdried with MgSO4
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-bae786dc6d744f6a93b1dfb97df71c62
Source dataset
uspto-grants-1990_09
Patent number
US04954503

Reaction notes

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