4-Fluorobenzylamine → N1-(4-Fluorobenzyl)-N4-(1H-5-indazolyl)-1,4-cyclohexanediamine

HRID 1352152

Reaction equation

HRID 1352152 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([NH:10][CH:11]3[CH2:16][CH2:15][C:14](=O)[CH2:13][CH2:12]3)=[CH:7][CH:8]=2)[CH:3]=[N:2]1.[F:18][C:19]1[CH:26]=[CH:25][C:22]([CH2:23][NH2:24])=[CH:21][CH:20]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl.CO>CO>[F:18][C:19]1[CH:26]=[CH:25][C:22]([CH2:23][NH:24][CH:14]2[CH2:15][CH2:16][CH:11]([NH:10][C:6]3[CH:5]=[C:4]4[C:9](=[CH:8][CH:7]=3)[NH:1][N:2]=[CH:3]4)[CH2:12][CH2:13]2)=[CH:21][CH:20]=1

Participants

6

Reactant 4

HCID 673264-FluorobenzylamineHCID 5049666Sodium triacetoxyborohydrideHCID 178382714-(1H-5-Indazolylamino)-1-cyclohexanone2×HCID 21893726Hydrochloride methanol

Product 1

HCID 17838166N1-(4-Fluorobenzyl)-N4-(1H-5-indazolyl)-1,4-cyclohexanediamineYield 23.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

4-(1H-5-Indazolylamino)-1-cyclohexanone (intermediate 3) (57 mg) and 4-fluorobenzylamine (70 mg) were dissolved in methanol (1 ml), and sodium triacetoxyborohydride (105 mg) was added by portions to the solution at room temperature. The reaction mixture was stirred at room temperature for 18 hr. Hydrochloric acid-methanol was then added thereto, and the mixture was stirred and was then concentrated. The residue was purified by HPLC [0.5% aqueous trifluoroacetic acid solution/acetonitrile]. A saturated aqueous sodium hydrogencarbonate solution (2 ml) was then added to fractions containing respective compounds, followed by extraction with chloroform-propanol (3/1). The organic layers were dried over anhydrous sodium sulfate, and the solvent was removed by distillation under the reduced pressure to give an anti-form compound (20 mg) and a syn-form compound (12 mg).

Workup

  1. stirringthe mixture was stirred
  2. concentrationwas then concentrated
  3. customThe residue was purified by HPLC [0.5% aqueous trifluoroacetic acid solution/acetonitrile]
  4. additionA saturated aqueous sodium hydrogencarbonate solution (2 ml) was then added to fractions
  5. additioncontaining respective compounds
  6. extractionfollowed by extraction with chloroform-propanol (3/1)
  7. dry with materialThe organic layers were dried over anhydrous sodium sulfate
  8. customthe solvent was removed by distillation under the reduced pressure

Sources & evidence

ORD record
ord-5f422201ad85448398f46459fe0c3b1b
Source dataset
uspto-grants-2007_05
Patent number
US07217722B2

Linked notes

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