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

HRID 1269881Notes

Reaction equation

HRID 1269881 reaction equation
C([BH3-])#N.[Na+].C(O)(=O)C.[CH3:9][S:10]([N:13]1[C:21]2[C:16](=[CH:17][C:18]([NH2:22])=[CH:19][CH:20]=2)[CH:15]=[N:14]1)(=[O:12])=[O:11].[CH2:23]([N:26]1[CH:31]2[CH2:32][CH2:33][CH:27]1[CH2:28][C:29](=O)[CH2:30]2)[CH2:24][CH3:25].[OH-].[Na+]>CO>[CH3:9][S:10]([N:13]1[C:21]2[C:16](=[CH:17][C:18]([NH:22][CH:29]3[CH2:28][CH:27]4[N:26]([CH2:23][CH2:24][CH3:25])[CH:31]([CH2:32][CH2:33]4)[CH2:30]3)=[CH:19][CH:20]=2)[CH:15]=[N:14]1)(=[O:11])=[O:12]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 5003444Sodium cyanoborohydrideHCID 229334151-(methylsulfonyl)-1H-indazol-5-amineHCID 233835798-Propyl-8-azabicyclo[3.2.1]octan-3-one

Product 1

HCID 184470781-(methylsulfonyl)-N-(8-propyl-8-azabicyclo[3.2.1]oct-3-yl)-1H-indazol-5-amineYield 3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Sodium cyanoborohydride (242 mg, 3.85 mmol) and then acetic acid (220 μl, 3.84 mmol) were added to a solution of 1-(methylsulfonyl)-1H-indazol-5-amine (163 mg, 0.772 mmol) and 8-propyl-8-azabicyclo[3.2.1]octan-3-one (150 mg, 0.924 mmol) in methanol (3 ml), and the resulting mixture was stirred at room temperature for 4 days. A 1N-aqueous sodium hydroxide solution 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 successively by a silica gel column chromatography (chloroform/methanol=4/1), a preparative thin-layer chromatography (200×200×0.5 mm, 2 plates, eluent: chloroform/methanol=4/1) and partition by LC/MS (water containing 0.05% trifluoroacetic acid-acetonitrile containing 0.035% trifluoroacetic acid, 10%–100% gradient, the extraction of the organic layer with aqueous ammonia/ethyl acetate after the partition) to obtain 1-(methylsulfonyl)-N-(8-propyl-8-azabicyclo[3.2.1]oct-3-yl)-1H-indazol-5-amine (8 mg, 3%).

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 successively by a silica gel column chromatography (chloroform/methanol=4/1)
  7. customa preparative thin-layer chromatography (200×200×0.5 mm, 2 plates, eluent: chloroform/methanol=4/1) and partition by LC/MS (water containing 0.05% trifluoroacetic acid-acetonitrile containing 0.035% trifluoroacetic acid, 10%–100% gradient
  8. extractionthe extraction of the organic layer with aqueous ammonia/ethyl acetate after the
  9. custompartition)

Sources & evidence

ORD record
ord-cda507f4dcb146da9de732424122b175
Source dataset
uspto-grants-2007_04
Patent number
US07199147B2

Reaction notes

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