Water → 5-[(1E)-4-{[tert-Butyl(dimethyl)silyl]oxy}but-1-en-1-yl]-1-(2,2-dimethylpropyl)-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

HRID 629909Notes

Reaction equation

HRID 629909 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.[C:17]([Si:21]([CH3:37])([CH3:36])[O:22][CH2:23][CH2:24]/[CH:25]=[CH:26]/B1OC(C)(C)C(C)(C)O1)([CH3:20])([CH3:19])[CH3:18].[C:38]([O-])([O-])=O.[Cs+].[Cs+].O>CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.O1CCOCC1>[Si:21]([O:22][CH2:23][CH2:24]/[CH:25]=[CH:26]/[C:2]1[N:7]=[C:6]2[N:8]([CH3:16])[C:9](=[O:15])[N:10]([CH2:11][C:12]([CH3:13])([CH3:14])[CH3:38])[C:5]2=[CH:4][CH:3]=1)([C:17]([CH3:18])([CH3:19])[CH3:20])([CH3:36])[CH3:37]

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 16217344(E)-tert-Butyldimethyl((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-en-1-yl)oxy)silaneHCID 772308275-chloro-1-(cyclopropylmethyl)-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

Product 1

HCID 1317353865-[(1E)-4-{[tert-Butyl(dimethyl)silyl]oxy}but-1-en-1-yl]-1-(2,2-dimethylpropyl)-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 312751,4-DioxaneSolvent

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, 1.0 g, 3.9 mmol, 1.0 equiv), tert-butyl(dimethyl){[(3E)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-en-1-yl]oxy}silane (32-1, 2.1 mL, 5.9 mmol, 1.5 equiv), Cs2CO3 (2.6 g, 7.9 mmol, 2.0 equiv) and Bis(tri-tert-butylphosphine)palladium(0) (0.40 g, 0.79 mmol, 0.2 equiv) were added to water (0.94 mL) and 1,4-dioxane (4.7 mL). The resulting mixture was heated to 100° C. and stirred for 18 h. Following this duration, LCMS showed 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 dark red oil. Purification by normal-phase HPLC (0-30% EtOAc:hexane) afforded 32-2 as an orange oil. MS m/z (M+H): calculated=404.2728; observed=404.2736.

Workup

  1. customconsumption of 1-4
  2. filtrationThe contents were filtered through Celite
  3. washwashed with ethyl acetate (10 mL)
  4. additionThe filtrate was diluted with saturated NaHCO3 (50 mL)
  5. customthe layers were separated
  6. extractionThe aqueous layer was back-extracted with ethyl acetate (3×20 mL)
  7. dry with materialthe combined organics were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give a dark red oil
  11. customPurification by normal-phase HPLC (0-30% EtOAc:hexane)

Sources & evidence

ORD record
ord-b9e24802a9e143a6b42983a6e8985bc5
Source dataset
uspto-grants-2016_04
Patent number
US09315518B2

Reaction notes

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