Acetic Acid → N-(8-propyl-8-azabicyclo[3.2.1]oct-3-yl)-1-tetrahydro-2H-pyran-2-yl-1H-indazol-5-amine

HRID 1269885Notes

Reaction equation

HRID 1269885 reaction equation
C([BH3-])#N.[Na+].C(O)(=O)C.[O:9]1[CH2:14][CH2:13][CH2:12][CH2:11][CH:10]1[N:15]1[C:23]2[C:18](=[CH:19][C:20]([NH2:24])=[CH:21][CH:22]=2)[CH:17]=[N:16]1.C(NC1C(C)=CC(C(OC)=O)=C(C)C=1)(=O)C.[CH2:41]([N:44]1[CH:49]2[CH2:50][CH2:51][CH:45]1[CH2:46][C:47](=O)[CH2:48]2)[CH2:42][CH3:43].N>CO>[CH2:41]([N:44]1[CH:49]2[CH2:50][CH2:51][CH:45]1[CH2:46][CH:47]([NH:24][C:20]1[CH:19]=[C:18]3[C:23](=[CH:22][CH:21]=1)[N:15]([CH:10]1[CH2:11][CH2:12][CH2:13][CH2:14][O:9]1)[N:16]=[CH:17]3)[CH2:48]2)[CH2:42][CH3:43]

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 222AmmoniaHCID 327521Methyl 4-acetamido-2,5-dimethylbenzoateHCID 5003444Sodium cyanoborohydrideHCID 229339271-(Oxan-2-yl)-1H-indazol-5-amineHCID 233835798-Propyl-8-azabicyclo[3.2.1]octan-3-one

Product 1

HCID 18447446N-(8-propyl-8-azabicyclo[3.2.1]oct-3-yl)-1-tetrahydro-2H-pyran-2-yl-1H-indazol-5-amineYield 73%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Sodium cyanoborohydride (484 mg, 7.70 mmol) and then acetic acid (440 μl, 7.68 mmol) were added to a solution of the 1-tetrahydro-2H-pyran-2-yl-1H-indazol-5-amine (335 mg, 1.54 mmol) obtained in Example 317, (e) and 8-propyl-8-azabicyclo[3.2.1]octan-3-one (300 mg, 1.85 mmol) in methanol (6 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=100/1/5) to obtain N-(8-propyl-8-azabicyclo[3.2.1]oct-3-yl)-1-tetrahydro-2H-pyran-2-yl-1H-indazol-5-amine (413 mg, 73%).

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=100/1/5)

Sources & evidence

ORD record
ord-9cd4676f9f144c9eb52ece0806781870
Source dataset
uspto-grants-2007_04
Patent number
US07199147B2

Reaction notes

Loading…