Isopropyl Acetate → tert-butyl 4-{2-oxo-1H,2H,3H-imidazo[4,5-b]pyridin-1-yl}piperidine-1-carboxylate

HRID 528027Notes

Reaction equation

HRID 528027 reaction equation
[NH2:1][C:2]1[C:7]([NH:8][CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)=[CH:6][CH:5]=[CH:4][N:3]=1.[C:22](C1NC=CN=1)(C1NC=CN=1)=[O:23].C(OC(C)C)(=O)C>C(#N)C>[O:23]=[C:22]1[NH:1][C:2]2=[N:3][CH:4]=[CH:5][CH:6]=[C:7]2[N:8]1[CH:9]1[CH2:10][CH2:11][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:13][CH2:14]1

Participants

5

Reactant 3

HCID 7915Isopropyl AcetateHCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 22293217tert-Butyl 4-[(2-aminopyridin-3-yl)amino]piperidine-1-carboxylate

Product 1

HCID 22293220tert-butyl 4-{2-oxo-1H,2H,3H-imidazo[4,5-b]pyridin-1-yl}piperidine-1-carboxylateYield 84%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

A 100 mL round bottom flask was charged with acetonitrile (20 mL, HPLC grade) and tert-butyl 4[(2-aminopyridin-3-yl)amino]piperidine-1-carboxylate (11, 1.89 g, 6.47 mmol) was added. Upon completion of addition, acetonitrile (5 mL) was added and the resulting suspension was stirred at room temperature for 30 minutes. Carbonyl diimidazole (1.57 g, 97.1 mmol) was then added over period of 10 minutes. The reaction mixture was heated to 50° C. and stirred overnight. The resulting solution was cooled to room temperature and concentrated under reduced pressure to give a brown solid. This solid was then mixed with 20 mL of isopropyl acetate and 20 mL of ice cold water. The resulting thick slurry was stirred overnight at room temperature. The brown solids were collected by vacuum filtration, washed with cold water (3×25 mL) and isopropyl acetate (3×25 mL) to give a light gray solid, which was dried to constant weight to give 1.73 g (84% yield) of tert-butyl 4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxylate. This material was submitted to the next step without further purification. 1H NMR (400 MHz, DMSO-d6): δ 11.56 (broad s, 1H), 7.89 (d, 1H), 7.54 (d, 1H), 6.98 (dd, 1H), 4.34 (m, 1H), 4.08 (broad m, 2H), 2.85 (broad m, 2H), 2.13 (m, 2H), 1.72 9 (d, 2H), 1.43 (s, 9H). MS (EI) for C16H22N4O3: 319 (MH+)

Workup

  1. additionwas added
  2. additionwas added
  3. temperatureThe reaction mixture was heated to 50° C.
  4. stirringstirred overnight
  5. temperatureThe resulting solution was cooled to room temperature
  6. concentrationconcentrated under reduced pressure
  7. customto give a brown solid
  8. stirringThe resulting thick slurry was stirred overnight at room temperature
  9. filtrationThe brown solids were collected by vacuum filtration
  10. washwashed with cold water (3×25 mL) and isopropyl acetate (3×25 mL)
  11. customto give a light gray solid, which
  12. customwas dried to constant weight

Sources & evidence

ORD record
ord-a902ba85582d4abdbf474f307671bc37
Source dataset
uspto-grants-2016_05
Patent number
US09346807B2

Reaction notes

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