Ammonia → 4-Bromo-6,7-dihydro-5H-cyclopenta[C]pyridin-7-amine

HRID 530325Notes

Reaction equation

HRID 530325 reaction equation
[Br:1][C:2]1[C:3]2[CH2:10][CH2:9][C:8](=O)[C:4]=2[CH:5]=[N:6][CH:7]=1.[NH3:12].CO.[BH4-].[Na+]>CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[Br:1][C:2]1[C:3]2[CH2:10][CH2:9][CH:8]([NH2:12])[C:4]=2[CH:5]=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 222AmmoniaHCID 887MethanolHCID 4311764Sodium borohydrideHCID 717438924-bromo-5H,6H,7H-cyclopenta[c]pyridin-7-one

Product 1

HCID 717438934-Bromo-6,7-dihydro-5H-cyclopenta[C]pyridin-7-amineYield 52%

Reagents, catalysts & solvents 1

HCID 11026Titanium isopropoxideCatalyst

Conditions

Temperature
0 °C

Procedure

4-Bromo-5H-cyclopenta[c]pyridin-7(6H)-one (1.01 g, 4.76 mmol), titanium (IV) isopropoxide (2.79 mL, 9.53 mmol) and ammonia, 2M in MeOH (11.9 mL, 23.8 mmol) were stirred at RT for 5 h. The reaction mixture was cooled to 0° C. and NaBH4 (270 mg, 7.14 mmol) was added in three portions over 20 min; the resulting mixture was stirred at RT for an additional 1.5 h. The reaction was quenched by pouring it into ammonium hydroxide (25%) (24.8 mL, pH 9-10), the precipitate was filtered and washed with AcOEt (3×, each time suspended in AcOEt and stirred for 5 min). The organic layer was separated and the remaining aqueous layer was extracted with EtOAc. The combined organic extracts were extracted with aq. 1 M HCl. The acidic aqueous extracts were washed with EtOAc (1×), then treated with aq. sodium hydroxide (2 M) to give a pH of 10-12, and extracted with EtOAc (3×). The combined organic extracts were washed with brine, dried (Na2SO4) and concentrated in vacuo to afford the title compound (530 mg, 52% yield in 70% purity, determined by 1H-NMR) as dark green amorphous solid. MS: 213.0 (M+H+, 1Br).

Workup

  1. customThe reaction was quenched
  2. additionby pouring it into ammonium hydroxide (25%) (24.8 mL, pH 9-10)
  3. filtrationthe precipitate was filtered
  4. washwashed with AcOEt (3×
  5. stirringstirred for 5 min)
  6. customThe organic layer was separated
  7. extractionthe remaining aqueous layer was extracted with EtOAc
  8. extractionThe combined organic extracts were extracted with aq. 1 M HCl
  9. washThe acidic aqueous extracts were washed with EtOAc (1×)
  10. additiontreated with aq. sodium hydroxide (2 M)
  11. customto give a pH of 10-12
  12. extractionextracted with EtOAc (3×)
  13. washThe combined organic extracts were washed with brine
  14. dry with materialdried (Na2SO4)
  15. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-81b2e4516dc44667bb334acfafecb168
Source dataset
uspto-grants-2016_05
Patent number
US09353081B2

Reaction notes

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