Cesium carbonate → 1-(2,2-Dimethylpropyl)-5-ethenyl-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

HRID 629904Notes

Reaction equation

HRID 629904 reaction equation
Cl[C:2]1[N:7]=[C:6]2[N:8]([CH3:16])[C:9](=[O:15])[N:10]([CH2:11][CH:12]3[CH2:14][CH2:13]3)[C:5]2=[CH:4][CH:3]=1.[CH:17]([B-](F)(F)F)=[CH2:18].[K+].[C:24]([O-])([O-])=O.[Cs+].[Cs+].O1CCOCC1>O>[CH3:24][C:12]([CH3:13])([CH3:14])[CH2:11][N:10]1[C:5]2[C:6](=[N:7][C:2]([CH:17]=[CH2:18])=[CH:3][CH:4]=2)[N:8]([CH3:16])[C:9]1=[O:15]

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 23679353Potassium vinyltrifluoroborateHCID 772308275-chloro-1-(cyclopropylmethyl)-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

Product 1

HCID 893046641-(2,2-Dimethylpropyl)-5-ethenyl-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

5-Chloro-1-(2,2-dimethylpropyl)-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (1-4, 3 g, 11.8 mmol, 1.0 equiv), potassium vinyltrifluoroborate (31-1, 3.2 g, 23.7 mmol, 2.0 equiv), Cs2CO3 (11.6 g, 35.5 mmol, 3.0 equiv) and 1,1′-bis(diphenylphosphino)-ferrocene-palladium(II)dichloride dichloromethane complex (0.97 g, 1.2 mmol, 0.10 equiv) were added to 1,4-dioxane (19.7 mL) and water (3.9 mL). The resulting reaction mixture was heated to 100° C. and stirred for 18 h. Following this duration, LCMS showed complete consumption of 1-4. The contents were filtered through Celite and washed with ethyl acetate (10 mL). The filtrate was diluted with saturated NaHCO3 (50 mL) and the layers were separated. The aqueous layer was back-extracted with ethyl acetate (3×20 mL) and the combined organics were dried over Na2SO4, filtered and concentrated in vacuo to give a brown semi-solid. Purification by normal-phase HPLC (0-40% EtOAc:hexane) afforded 31-2 as a yellow solid. MS m/z (M+H): calculated=246.1601; observed=246.1608.

Workup

  1. customThe resulting reaction mixture
  2. customconsumption of 1-4
  3. filtrationThe contents were filtered through Celite
  4. washwashed with ethyl acetate (10 mL)
  5. additionThe filtrate was diluted with saturated NaHCO3 (50 mL)
  6. customthe layers were separated
  7. extractionThe aqueous layer was back-extracted with ethyl acetate (3×20 mL)
  8. dry with materialthe combined organics were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto give a brown semi-solid
  12. customPurification by normal-phase HPLC (0-40% EtOAc:hexane)

Sources & evidence

ORD record
ord-fbfea340c4fd43419122553f3282ab5a
Source dataset
uspto-grants-2016_04
Patent number
US09315518B2

Reaction notes

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