Cesium carbonate → 1-(2,2-Dimethylpropyl)-5-[2-(4-methoxyphenyl)-6-methyl-2-azabicyclo-[2.2.2]oct-5-en-5-yl]-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

HRID 629869Notes

Reaction equation

HRID 629869 reaction equation
FC(F)(F)S(O[C:7]1[CH:8]2[CH2:15][CH2:14][CH:11]([C:12]=1[CH3:13])[N:10]([C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=1)[CH2:9]2)(=O)=O.[C:26]([O-])(=O)C.[K+].Cl[C:32]1[N:37]=[C:36]2[N:38]([CH3:46])[C:39](=[O:45])[N:40]([CH2:41][CH:42]3[CH2:44][CH2:43]3)[C:35]2=[CH:34][CH:33]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].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.O.O1CCOCC1>[CH3:26][C:42]([CH3:43])([CH3:44])[CH2:41][N:40]1[C:35]2[C:36](=[N:37][C:32]([C:7]3[CH:8]4[CH2:15][CH2:14][CH:11]([C:12]=3[CH3:13])[N:10]([C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=3)[CH2:9]4)=[CH:33][CH:34]=2)[N:38]([CH3:46])[C:39]1=[O:45]

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 517044Potassium AcetateHCID 772308275-chloro-1-(cyclopropylmethyl)-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-oneHCID 892876732-(4-Methoxyphenyl)-6-methyl-2-azabicyclo[2.2.2]oct-5-en-5-yl trifluoromethanesulfonate

Product 1

HCID 1177023811-(2,2-Dimethylpropyl)-5-[2-(4-methoxyphenyl)-6-methyl-2-azabicyclo-[2.2.2]oct-5-en-5-yl]-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 178418851HCID 178418851, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

2-(4-Methoxyphenyl)-6-methyl-2-azabicyclo[2.2.2]oct-5-en-5-yl trifluoromethanesulfonate (7-2, 429 mg, 1.14 mmol, 1.0 equiv), bis(pinocolato)diboron (317 mg, 1.25 mmol, 1.1 equiv), potassium acetate (334 mg, 3.41 mmol, 3.0 equiv) and PdCl2(dppf) (58.2 mg, 0.079 mmol, 0.07 equiv) were added to anhydrous 1,4-dioxane (1.4 mL) and heated to 60° C. After 18 h, the reaction contents were cooled to RT, followed by the subsequent addition of water (289 μL), 5-chloro-1-(2,2-dimethylpropyl)-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]-pyridin-2-one (1-4, 288 mg, 1.14 mmol, 1.0 equiv), Cs2CO3 (744 mg, 2.28 mmol, 2.01 equiv) and Bis(tri-tert-butylphosphine)palladium(0) (75 mg, 0.148 mmol, 0.13 equiv). The resulting mixture was heated to 60° C. for 4.5 h. Following this duration, LCMS showed consumption of starting material. The contents were then cooled to room temperature, diluted with ethyl acetate (10 mL), filtered through Celite and rinsed with ethyl acetate (3×7 mL) and water (1×3 mL).

Workup

  1. customthe reaction contents
  2. temperaturewere cooled to RT
  3. temperatureThe resulting mixture was heated to 60° C. for 4.5 h
  4. customconsumption of starting material
  5. temperatureThe contents were then cooled to room temperature
  6. additiondiluted with ethyl acetate (10 mL)
  7. filtrationfiltered through Celite
  8. washrinsed with ethyl acetate (3×7 mL) and water (1×3 mL)

Sources & evidence

ORD record
ord-e09bc3e95d654762aec10efcc33ca5a0
Source dataset
uspto-grants-2016_04
Patent number
US09315518B2

Reaction notes

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