Bromocycloheptane → 3-Cycloheptyl-3H-imidazo[4,5-b]pyridin-5-ol

HRID 1890279Notes

Reaction equation

HRID 1890279 reaction equation
C([O:8][C:9]1[N:14]=[C:13]2[NH:15][CH:16]=[N:17][C:12]2=[CH:11][CH:10]=1)C1C=CC=CC=1.[H-].[Na+].Br[CH:21]1[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1>C1COCC1.CCOCC>[CH:21]1([N:15]2[C:13]3=[N:14][C:9]([OH:8])=[CH:10][CH:11]=[C:12]3[N:17]=[CH:16]2)[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1

Participants

6

Reactant 3

HCID 16992BromocycloheptaneHCID 24758Sodium hydrideHCID 178420377HCID 178420377, compound

Product 1

HCID 1785157653-Cycloheptyl-3H-imidazo[4,5-b]pyridin-5-olYield 17.3%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

5-(Benzyloxy)-3H-imidazo[4,5-b]pyridine (2.00 g, 8.88 mmol) was dissolved in THF and NaH (0.18 g, 14.7 mmol) was added portionwise. The resulting mixture was heated in a sealed tube for 1 h and then cooled to room temperature. Bromocycloheptane (3.14 g, 17.8 mmol) was added and the reaction was heated to 70° C. overnight. The solution was then diluted with ether and washed with water. The aqueous layer was back extracted with additional ether and the combined organic portions were washed with brine, dried over MgSO4 and purified by preparative HPLC. The resulting 5-(benzyloxy)-3-cycloheptyl-3H-imidazo[4,5-b]pyridine was then dissolved in MeOH with catalytic amount of 5% Pd/C and excess ammonium formate. The reaction mixture was heated to 80° C. until the reaction was complete. The solvent was removed under reduced pressure and the residue purified via preparative HPLC to give the title compound (0.356 g). LCMS m/z=232.1 [M+H]+; 1H NMR (400 MHz, acetonitrile-d3) δ ppm 1.55-1.80 (m, 6H), 1.80-1.90 (m, 2H), 2.05-2.20 (m, 4H), 4.50-4.60 (m, 1H), 6.57 (d, J=8.6 Hz, 1H), 7.85 (d, J=8.6 Hz, 1H), 7.96 (s, 1H).

Workup

  1. temperatureThe resulting mixture was heated in a sealed tube for 1 h
  2. temperaturethe reaction was heated to 70° C. overnight
  3. washwashed with water
  4. extractionThe aqueous layer was back extracted with additional ether
  5. washthe combined organic portions were washed with brine
  6. dry with materialdried over MgSO4
  7. custompurified by preparative HPLC
  8. dissolutionThe resulting 5-(benzyloxy)-3-cycloheptyl-3H-imidazo[4,5-b]pyridine was then dissolved in MeOH with catalytic amount of 5% Pd/C and excess ammonium formate
  9. temperatureThe reaction mixture was heated to 80° C. until the reaction
  10. customThe solvent was removed under reduced pressure
  11. customthe residue purified via preparative HPLC

Sources & evidence

ORD record
ord-965cb245fd3d46f485e9c63faa0255f9
Source dataset
uspto-grants-2013_08
Patent number
US08507473B2

Reaction notes

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