Sodium hydride → tert-butyl 4-(7-iodo-2H-pyrazolo[4,3-b]pyridin-2-yl)piperidine-1-carboxylate

HRID 1522611Notes

Reaction equation

HRID 1522611 reaction equation
[H-].[Na+].[I:3][C:4]1[CH:9]=[CH:8][N:7]=[C:6]2[CH:10]=[N:11][NH:12][C:5]=12.Br[CH:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1>CN(C=O)C>[I:3][C:4]1[C:5]2[C:6](=[CH:10][N:11]([CH:14]3[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]3)[N:12]=2)[N:7]=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 15541517tert-Butyl 4-bromopiperidine-1-carboxylateHCID 674695597-iodo-1H-pyrazolo[4,3-b]pyridine

Product 1

HCID 67469655tert-butyl 4-(7-iodo-2H-pyrazolo[4,3-b]pyridin-2-yl)piperidine-1-carboxylateYield 13%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (55.2 mg, 1.379 mmol) was added to a solution of 7-iodo-1H-pyrazolo[4,3-b]pyridine (260 mg, 1.061 mmol) in DMF (1.5 mL) at 0° C., and the reaction was stirred for 5 minutes. tert-Butyl 4-bromopiperidine-1-carboxylate (364 mg, 1.379 mmol) was added and the reaction was warmed to room temperature and then heated at 65° C. for 2 hours. The reaction was cooled, quenched with water, and concentrated in vacuo. The residue was partitioned between saturated NH4Cl solution and EtOAc. The organic layer was separated, dried over Na2SO4, and concentrated in vacuo to afford a residue. The residue was purified with silica column chromatography eluted with hexanes/ethyl acetate step gradient (0-100% EtOAc over 45 minutes), to afford tert-butyl 4-(7-iodo-2H-pyrazolo[4,3-b]pyridin-2-yl)piperidine-1-carboxylate (57 mg, 13%). The fractions containing tert-butyl 4-(7-iodo-1H-pyrazolo[4,3-b]pyridin-1-yl)piperidine-1-carboxylate were chromatographed again under the same conditions to give tert-butyl 4-(7-iodo-1H-pyrazolo[4,3-b]pyridin-1-yl)piperidine-1-carboxylate (60 mg, 13%). MS [M+H] found 429.2

Workup

  1. temperatureheated at 65° C. for 2 hours
  2. temperatureThe reaction was cooled
  3. customquenched with water
  4. concentrationconcentrated in vacuo
  5. customThe residue was partitioned between saturated NH4Cl solution and EtOAc
  6. customThe organic layer was separated
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. customto afford a residue
  10. customThe residue was purified with silica column chromatography
  11. washeluted with hexanes/ethyl acetate step gradient (0-100% EtOAc over 45 minutes)

Sources & evidence

ORD record
ord-1fc86565c8934f48a41002eba2794163
Source dataset
uspto-grants-2015_07
Patent number
US09073918B2

Reaction notes

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