Acetic Acid → N-Cyclohexyl-2-phenyl-2H-indazol-3-amine

HRID 1690507Notes

Reaction equation

HRID 1690507 reaction equation
[C:1]1([N:7]2[C:15]([NH2:16])=[C:14]3[C:9]([CH:10]=[CH:11][CH:12]=[CH:13]3)=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:17]1(=O)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH:17]1([NH:16][C:15]2[N:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[N:8]=[C:9]3[C:14]=2[CH:13]=[CH:12][CH:11]=[CH:10]3)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 7967CyclohexanoneHCID 5049666Sodium triacetoxyborohydrideHCID 132308592-Phenyl-2H-indazol-3-amine

Product 1

HCID 12318206N-Cyclohexyl-2-phenyl-2H-indazol-3-amineYield 18%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-phenyl-2H-indazol-3-amine (800 mg, 4 mmol; Shirtcliff, Laura D.; Rivers, Jazmin; Haley, Michael M, Journal of Organic Chemistry (2006), 71(17), 6619-6622) in CH2Cl2 (43 ml) was added cyclohexanone (1.97 ml, 19 mmol; [108-94-1]), acetic acid (0.22 ml, 4 mmol) and sodium triacetoxyborohydride (2.43 g, 11 mmol) at ambient temperature under an argon atmosphere. The reaction mixture was heated under reflux conditions for 12 h, poured onto ice water/aqueous NaHCO3 solution 1/1 and extracted two times with CH2Cl2. The combined extracts were washed with ice water/brine 1/1 and dried over Na2SO4. After filtration the solvent was removed under reduced pressure, the resulting brown oil was dissolved in MeOH (20 ml) and heated under reflux conditions for 30 min. Removal of the solvent under reduced pressure left a brown oil which was purified by column chromatography (silica gel, iPrOAc/heptane) to give the title compound (206 mg, 0.7 mmol; 18%) as yellow oil. MS: m/e=292.4 [M+H+].

Workup

  1. temperatureThe reaction mixture was heated under reflux conditions for 12 h
  2. additionpoured onto ice water/aqueous NaHCO3 solution 1/1
  3. extractionextracted two times with CH2Cl2
  4. washThe combined extracts were washed with ice water/brine 1/1
  5. dry with materialdried over Na2SO4
  6. filtrationAfter filtration the solvent
  7. customwas removed under reduced pressure
  8. dissolutionthe resulting brown oil was dissolved in MeOH (20 ml)
  9. temperatureheated under reflux conditions for 30 min
  10. customRemoval of the solvent under reduced pressure
  11. waitleft a brown oil which
  12. customwas purified by column chromatography (silica gel, iPrOAc/heptane)

Sources & evidence

ORD record
ord-455e896b3cbe40608c7cada7850b5a3c
Source dataset
uspto-grants-2012_04
Patent number
US08153663B2

Reaction notes

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