Acetic Acid → 3-bromo-N-(8-propyl-8-azabicyclo[3.2.1]oct-3-yl)-1H-indazol-5-amine

HRID 1269884Notes

Reaction equation

HRID 1269884 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C.[Br:19][C:20]1[C:28]2[C:23](=[CH:24][CH:25]=[C:26]([NH2:29])[CH:27]=2)[NH:22][N:21]=1.[CH2:30]([N:33]1[CH:38]2[CH2:39][CH2:40][CH:34]1[CH2:35][C:36](=O)[CH2:37]2)[CH2:31][CH3:32].N>ClC(Cl)C>[Br:19][C:20]1[C:28]2[C:23](=[CH:24][CH:25]=[C:26]([NH:29][CH:36]3[CH2:35][CH:34]4[N:33]([CH2:30][CH2:31][CH3:32])[CH:38]([CH2:39][CH2:40]4)[CH2:37]3)[CH:27]=2)[NH:22][N:21]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 222AmmoniaHCID 5049666Sodium triacetoxyborohydrideHCID 233835798-Propyl-8-azabicyclo[3.2.1]octan-3-oneHCID 178507356HCID 178507356, compound

Product 1

HCID 1784561453-bromo-N-(8-propyl-8-azabicyclo[3.2.1]oct-3-yl)-1H-indazol-5-amineYield 1.1%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

Sodium triacetoxyborohydride (159 mg, 0.750 mmol) and then acetic acid (29 μl, 0.507 mmol) were added to a suspension of 3-bromo-1H-indazol-5-amine (106 mg, 0.500 mmol) and 8-propyl-8-azabicyclo[3.2.1]octan-3-one (100 mg, 0.598 mmol) in dichloroethane (3 ml), and the resulting mixture was stirred at room temperature for 1 day. Aqueous ammonia was added thereto, followed by extraction with ethyl acetate. The extract solution was washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate, and then distilled under reduced pressure to remove the solvent. The residue was purified by a silica gel column chromatography (chloroform/methanol/triethylamine=100/10/5) and a preparative thin-layer chromatography (200×200×0.5 mm, eluent: chloroform/methanol/triethylamine=100/5/5) to obtain 3-bromo-N-(8-propyl-8-azabicyclo[3.2.1]oct-3-yl)-1H-indazol-5-amine (2 mg, 1%).

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe extract solution was washed with a saturated aqueous sodium chloride solution
  3. dry with materialdried over sodium sulfate
  4. distillationdistilled under reduced pressure
  5. customto remove the solvent
  6. customThe residue was purified by a silica gel column chromatography (chloroform/methanol/triethylamine=100/10/5)

Sources & evidence

ORD record
ord-c31c08dac4f14100885625d339085a5e
Source dataset
uspto-grants-2007_04
Patent number
US07199147B2

Reaction notes

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