Cesium carbonate → Benzyl {3-[1-(2,2-dimethylpropyl)-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl]-6,6-dimethylcyclohex-2-en-1-yl}carbamate

HRID 629884Notes

Reaction equation

HRID 629884 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]([O-])([O-])=O.[Cs+].[Cs+].[CH3:23][C:24]1([CH3:50])[CH:29]([NH:30][C:31](=[O:40])[O:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH:28]=[C:27](B2OC(C)(C)C(C)(C)O2)[CH2:26][CH2:25]1.O1CCOCC1>CO.CN1C(=O)CCC1.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>[CH3:17][C:12]([CH3:13])([CH3:14])[CH2:11][N:10]1[C:5]2[C:6](=[N:7][C:2]([C:27]3[CH2:26][CH2:25][C:24]([CH3:23])([CH3:50])[CH:29]([NH:30][C:31](=[O:40])[O:32][CH2:33][C:34]4[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=4)[CH:28]=3)=[CH:3][CH:4]=2)[N:8]([CH3:16])[C:9]1=[O:15]

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 71135221Benzyl [6,6-dimethyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-2-en-1-yl]carbamateHCID 772308275-chloro-1-(cyclopropylmethyl)-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

Product 1

HCID 71135222Benzyl {3-[1-(2,2-dimethylpropyl)-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl]-6,6-dimethylcyclohex-2-en-1-yl}carbamate

Reagents, catalysts & solvents 4

HCID 178418851HCID 178418851, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
100 °C

Procedure

To a microwave vial was added 5-chloro-1-(2,2-dimethylpropyl)-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (1-4) (313 mg, 1.234 mmol), Cs2CO3 (804 mg, 2.467 mmol), benzyl [6,6-dimethyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-2-en-1-yl]carbamate (668 mg, 1.734 mmol), & bis(tri-t-butylphosphine)palladium(0) (129 mg, 0.252 mmol), followed by anhydrous 1,4-dioxane (2.5 mL) & water (0.5 mL). The reaction mixture was then heated to 100° C. for 2×10 minutes under microwave irradiation. The reaction was then cooled to room temperature, diluted with MeOH & NMP, filtered & resulting residue was purified by reverse-phase chromatography (10-100% CH3CN:0.1% TFA in H2O) to yield benzyl {3-[1-(2,2-dimethylpropyl)-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl]-6,6-dimethylcyclohex-2-en-1-yl}carbamate (16-1) as a white solid/foam. HRMS m/z (M+H): calculated=477.2860; observed=477.2865.

Workup

  1. temperatureThe reaction was then cooled to room temperature
  2. filtrationfiltered
  3. customresulting residue
  4. customwas purified by reverse-phase chromatography (10-100% CH3CN:0.1% TFA in H2O)

Sources & evidence

ORD record
ord-0dd5149243f748fba9354c883fbd014d
Source dataset
uspto-grants-2016_04
Patent number
US09315518B2

Reaction notes

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