2-Aminopyridine → Tert-butyl 4-(imidazo[1,2-a]pyridin-3-yl)piperidine-1-carboxylate

HRID 1068211Notes

Reaction equation

HRID 1068211 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14](Br)[CH:15]=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=1>C(O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[N:20]3[CH:21]=[CH:22][CH:23]=[CH:24][C:19]3=[N:18][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 104392-AminopyridineHCID 21912701tert-Butyl 4-(1-bromo-2-oxoethyl)piperidine-1-carboxylate

Product 1

HCID 21912736Tert-butyl 4-(imidazo[1,2-a]pyridin-3-yl)piperidine-1-carboxylateYield 35.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 1.15 g of 1-(t-butoxycarbonyl)-4-(1-bromo-2-oxoethyl)-piperidine (from Example 292, Step C) in 15 mL ethanol was added 388 mg of 2-aminopyridine. After refluxing for 18 hours, the solvent was evaporated. The mixture was partitioned between EtOAc and saturated sodium bicarbonate solution. Aqueous layer was extracted with EtOAc (3×). The combined organic phase was washed with brine, dried over MgSO4 and concentrated. The residue was purified by flash chromatography with 50% EtOAc in hexanes, followed by 100% EtOAc to give 401 mg of the title compound as a solid. 1H NMR (500 MHz, CDCl3) δ1.48 (s, 9H), 1.70 (m, 2H), 2.06 (d, J=13 Hz, 2H), 2.93-3.02 (m, 3H), 4.26 (br, 2H), 6.87 (t, J=6.8 Hz, 1H). 7.21(m, 1H), 7.44(s, 1H), 7. 69(d, J=9.2 Hz,1H), 7.99 (d, J=6.9 Hz, 1H).

Workup

  1. temperatureAfter refluxing for 18 hours
  2. customthe solvent was evaporated
  3. customThe mixture was partitioned between EtOAc and saturated sodium bicarbonate solution
  4. extractionAqueous layer was extracted with EtOAc (3×)
  5. washThe combined organic phase was washed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography with 50% EtOAc in hexanes

Sources & evidence

ORD record
ord-2bbce8f8bd87438baef10284ee65b51c
Source dataset
uspto-grants-2001_06
Patent number
US06248755B1

Reaction notes

Loading…