Hydrochloric Acid → 1-(piperidin-4-yl)-1H,2H,3H-imidazo[4,5-b]pyridin-2-one dihydrochloride

HRID 528028Notes

Reaction equation

HRID 528028 reaction equation
[O:1]=[C:2]1[NH:10][C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[N:3]1[CH:11]1[CH2:16][CH2:15][N:14](C(OC(C)(C)C)=O)[CH2:13][CH2:12]1.[ClH:24]>CO>[ClH:24].[ClH:24].[NH:14]1[CH2:13][CH2:12][CH:11]([N:3]2[C:4]3[C:5](=[N:6][CH:7]=[CH:8][CH:9]=3)[NH:10][C:2]2=[O:1])[CH2:16][CH2:15]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 22293220tert-butyl 4-{2-oxo-1H,2H,3H-imidazo[4,5-b]pyridin-1-yl}piperidine-1-carboxylate

Product 1

HCID 222931811-(piperidin-4-yl)-1H,2H,3H-imidazo[4,5-b]pyridin-2-one dihydrochlorideYield 84%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A 50 mL 3-necked round bottom flask fitted with a thermometer, was charged with 30 mL of methanol (HPLC grade), and tert-butyl 4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxylate (1.71 g, 5.37 mmol) was then added over a period of 5 minutes. The resulting brown suspension was stirred at room temperature for 30 minutes. Hydrogen chloride gas (Reagent Plus, steel cylinder, Aldrich) was carefully bubbled into the reaction mixture, resulting in a dark brown solution (Note: the temperatures of the reaction mixture rises to 38° C.). The flow of gas was stopped when the reaction mixture was saturated with hydrogen chloride. After 20 minutes a solid precipitated out of solution, and the resulting slurry was cooled to room temperature. The progress of the reaction was monitored by LCMS. The reaction was complete in 6 hours. The reaction mixture was diluted with isopropyl acetate (25 mL) and stirred for an additional 30 minutes; the solids were then collected by vacuum filtration. The resulting brown solid was washed with isopropyl acetate (5 mL), and dried to constant weight to give 1.32 g (84% yield) of 1-piperidin-4-yl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one dihydrochloride. This material was submitted to the next step without further purification. 1H NMR (400 MHz, DMSO-d6): δ 11.77 (broad s, 1H), 8.32 (broad s, 3H), 7.95 (d, 1H), 7.93 (s, 1H), 7.06 (dd, 1H), 4.60 (m, 1H), 3.39 (d, 2H), 3.07 (q, 2H), 3.65 (dq, 2H), 1.86 (d, 2H). MS (EI) for C11H14N4; 219 (MH+)

Workup

  1. customA 50 mL 3-necked round bottom flask fitted with a thermometer
  2. additionwas then added over a period of 5 minutes
  3. customHydrogen chloride gas (Reagent Plus, steel cylinder, Aldrich) was carefully bubbled into the reaction mixture
  4. customresulting in a dark brown solution (Note
  5. customrises to 38° C.
  6. customAfter 20 minutes a solid precipitated out of solution
  7. temperaturethe resulting slurry was cooled to room temperature
  8. waitThe reaction was complete in 6 hours
  9. additionThe reaction mixture was diluted with isopropyl acetate (25 mL)
  10. stirringstirred for an additional 30 minutes
  11. filtrationthe solids were then collected by vacuum filtration
  12. washThe resulting brown solid was washed with isopropyl acetate (5 mL)
  13. customdried to constant weight

Sources & evidence

ORD record
ord-d8413a552eb24d9da306f4b3dc6d7cc0
Source dataset
uspto-grants-2016_05
Patent number
US09346807B2

Reaction notes

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