Ammonium Chloride → Tert-butyl 3-((5-amino-2-bromopyridin-4-yl)amino)piperidine-1-carboxylate

HRID 919644Notes

Reaction equation

HRID 919644 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([NH:8][CH:9]2[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10]2)[C:5]([N+:22]([O-])=O)=[CH:4][N:3]=1.[NH4+].[Cl-].CCO.O>C(Cl)Cl.[Fe]>[NH2:22][C:5]1[C:6]([NH:8][CH:9]2[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10]2)=[CH:7][C:2]([Br:1])=[N:3][CH:4]=1

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 19096565Water ethanolHCID 86706484Tert-butyl 3-((2-bromo-5-nitropyridin-4-yl)amino)piperidine-1-carboxylate

Product 1

HCID 86706485Tert-butyl 3-((5-amino-2-bromopyridin-4-yl)amino)piperidine-1-carboxylateYield 100%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 6344DichloromethaneSolvent

Procedure

To a mixture of tert-butyl 3-((2-bromo-5-nitropyridin-4-yl)amino)piperidine-1-carboxylate. (1.24 g, 3.01 mmol, 1.0 eq) and NH4Cl (2.43 g, 45 mmol, 15 eq) was added a 2:1 mixture EtOH/water (30 mL). The reaction mixture was heated to reflux, then iron powder (0.67 g, 12 mmol, 3.5 eq) was added in portions over 15 min and the suspension was continued to be heated at refluxed for 16 h. The reaction mixture was cooled to rt, diluted with CH2Cl2 (300 mL) and filtered through celite. The organic layer was washed with water (50 mL×2) and brine (50 mL), dried (Na2SO4), filtered and concentrated in vacuo to give the title compound (1.2 g, 100%) which was used to next step without further purification. 1H NMR (400 MHz, CDCl3) δ: 7.66 (s, 1H), 6.63 (s, 1H), 4.51-4.39 (m, 1H), 3.89-3.86 (m, 1H), 3.67-3.63 (m, 1H), 3.41-3.10 (m, 4H), 2.09-1.95 (m, 1H), 1.74-1.60 (m, 3H), 1.47 (s, 9H). ESI-MS (M+H+): 371.0.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux
  3. temperatureto be heated
  4. temperatureat refluxed for 16 h
  5. filtrationfiltered through celite
  6. washThe organic layer was washed with water (50 mL×2) and brine (50 mL)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-81f04cf7a8ed43f4b216428c048bafbd
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

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