Ammonium Acetate → (5S,6S,9R)-5-Azido-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-amine

HRID 589003Notes

Reaction equation

HRID 589003 reaction equation
[N:1]([C@@H:4]1[C:14]2[C:9](=[N:10][CH:11]=[CH:12][CH:13]=2)[C:8](=O)[CH2:7][CH2:6][C@H:5]1[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[C:17]=1[F:23])=[N+:2]=[N-:3].C([O-])(=O)C.[NH4+].C([BH3-])#[N:30].[Na+]>CO>[N:1]([C@@H:4]1[C:14]2[C:9](=[N:10][CH:11]=[CH:12][CH:13]=2)[C@H:8]([NH2:30])[CH2:7][CH2:6][C@H:5]1[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[C:17]=1[F:23])=[N+:2]=[N-:3]

Participants

5

Reactant 3

HCID 517165Ammonium AcetateHCID 5003444Sodium cyanoborohydrideHCID 117992047(5S,6S)-5-Azido-6-(2,3-difluorophenyl)-5,6,7,8-tetrahydro-9H-cyclohepta[b]pyridin-9-one

Product 1

HCID 117992070(5S,6S,9R)-5-Azido-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-amine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (5S,6S)-5-azido-6-(2,3-difluorophenyl)-5,6,7,8-tetrahydro-9H-cyclohepta[b]pyridin-9-one (190 mg, 0.60 mmol), and ammonium acetate (2.3 g, 30 mmol) in MeOH (10 mL) was added sodium cyanoborohydride (27 mg, 0.42 mmol) and the resulting mixture was stirred at ambient temperature for 16 h. The reaction mixture was concentrated under reduced pressure and the residue was partitioned between dichloromethane (20 mL) and aqueous 1 N NaOH solution (5 mL). The organic layer was separated, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography, eluting with a gradient of EtOAc:MeOH:Et3N-100:0:0 to 85:10:5, to give the title compound as a mixture of diastereomers. MS: m/z=316.2 (M+1).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customthe residue was partitioned between dichloromethane (20 mL) and aqueous 1 N NaOH solution (5 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with a gradient of EtOAc

Sources & evidence

ORD record
ord-afd500d6a6334048bc5996d534499a7c
Source dataset
uspto-grants-2016_01
Patent number
US09227973B2

Reaction notes

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