Cesium fluoride → 2-(Imidazo[1,2-a]pyrazin-3-yl)furo[2,3-c]pyridin-7-amine

HRID 389565Notes

Reaction equation

HRID 389565 reaction equation
C(OC([N:8]([C:16]1[N:17]=[CH:18][CH:19]=[C:20]2[CH:24]=[C:23]([Sn](C)(C)C)[O:22][C:21]=12)C(OC(C)(C)C)=O)=O)(C)(C)C.Br[C:30]1[N:34]2[CH:35]=[CH:36][N:37]=[CH:38][C:33]2=[N:32][CH:31]=1.[F-].[Cs+]>O1CCOCC1>[N:32]1[CH:31]=[C:30]([C:23]2[O:22][C:21]3=[C:16]([NH2:8])[N:17]=[CH:18][CH:19]=[C:20]3[CH:24]=2)[N:34]2[CH:35]=[CH:36][N:37]=[CH:38][C:33]=12

Participants

5

Reactant 3

HCID 25953Cesium fluorideHCID 27716713-Bromoimidazo(1,2-a)pyrazineHCID 66760488Di-tert-butyl[2-(trimethylstannanyl)furo[2,3-c]pyridin-7-yl]imidodicarbonate

Product 1

HCID 667602142-(Imidazo[1,2-a]pyrazin-3-yl)furo[2,3-c]pyridin-7-amineYield 49.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of di-tert-butyl[2-(trimethylstannanyl)furo[2,3-c]pyridin-7-yl]imidodicarbonate (0.0994 g, 0.200 mmol) in 1,4-dioxane (1.5 mL) was degassed with nitrogen for 10 min. To this mixture was added 3-bromoimidazo[1,2-a]pyrazine (0.033 g, 0.17 mmol), Pd(FPh3)4 (0.0192 g, 0.0167 mmol) and cesium fluoride (0.0850 g, 0.560 mmol). The temperature was raised to 100° C. and the mixture was heated for 16 h. Following removal of solvent, the residue was purified by ISCO chromatography (0 to 10% methanol:DCM). The resultant material was dissolved in dichloromethane (2 mL) and cooled to 0° C. To this mixture was slowly added TFA (2 mL). The ice bath was removed and the mixture was stirred for 2 h and then concentrated to a light brown residue. The residue was dissolved in DCM (30 mL) and saturated aqueous sodium bicarbonate (5 mL) was added and then the mixture was concentrated. Purification by ISCO chromatography (0 to 20% methanol:DCM) afforded 0.021 g (49%) of the title compound as an off-white solid. 1H NMR (400 MHz, CD3OD): δ=9.19 (dd, J=1.4, 4.7 Hz, 1 H), 9.17 (d, J=1.5 Hz, 1 H), 8.46 (s, 1 H), 7.76 (dd, J=4.3, 5.6 Hz, 2 H), 7.43 (s, 1 H), 7.37 (s, 1 H); MS (ESI): 252.17 [M+H]+.

Workup

  1. customwas degassed with nitrogen for 10 min
  2. temperaturethe mixture was heated for 16 h
  3. customremoval of solvent
  4. customthe residue was purified by ISCO chromatography (0 to 10% methanol:DCM)
  5. dissolutionThe resultant material was dissolved in dichloromethane (2 mL)
  6. temperaturecooled to 0° C
  7. customThe ice bath was removed
  8. concentrationconcentrated to a light brown residue
  9. dissolutionThe residue was dissolved in DCM (30 mL)
  10. additionsaturated aqueous sodium bicarbonate (5 mL) was added
  11. concentrationthe mixture was concentrated
  12. customPurification by ISCO chromatography (0 to 20% methanol:DCM)

Sources & evidence

ORD record
ord-08e113e7f06a472da079daca92abab42
Source dataset
uspto-grants-2013_02
Patent number
US08378104B2

Reaction notes

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