Bromocyclopentane → 3-Cyclopentyl-3H-imidazo[4,5-b]pyridin-5-ol

HRID 1890280Notes

Reaction equation

HRID 1890280 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[CH2:25][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)[CH2:25][CH2:24][CH2:23][CH2:22]1

Participants

6

Reactant 3

HCID 8728BromocyclopentaneHCID 24758Sodium hydrideHCID 178420377HCID 178420377, compound

Product 1

HCID 1785157563-Cyclopentyl-3H-imidazo[4,5-b]pyridin-5-olYield 10.5%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

5-(Benzyloxy)-3H-imidazo[4,5-b]pyridine (0.300 g, 1.33 mmol) was dissolved in THF and NaH (0.050 g, 2.0 mmol) was added portionwise. The resulting mixture was heated in a sealed tube for 1 h and then cooled to room temperature. Bromocyclopentane (0.20 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 DCM and diluted with excess sulfuric acid. The resulting solution was stirred for 30 minutes at room temperature then acidified with the addition of 1 M aqueous hydrochloric acid. The solvent was removed from the organic layer and the residue was purified via preparative HPLC to give the title compound (0.0284 g). LCMS m/z=204.31 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.65-1.80 (m, 2H), 1.80-1.95 (m, 2H), 2.0-2.1 (m, 2H), 2.15-2.30 (m, 2H), 4.95-5.05 (m, 1H), 6.88 (d, J=8.8 Hz, 1H), 8.13 (d, J=8.8 Hz, 1H), 9.35 (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 DCM
  9. additiondiluted with excess sulfuric acid
  10. additionthen acidified with the addition of 1 M aqueous hydrochloric acid
  11. customThe solvent was removed from the organic layer
  12. customthe residue was purified via preparative HPLC

Sources & evidence

ORD record
ord-2593f03e94724eb2b4cd54b304a1c499
Source dataset
uspto-grants-2013_08
Patent number
US08507473B2

Reaction notes

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