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

HRID 629885Notes

Reaction equation

HRID 629885 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+].CC1(C)C(C)(C)OB([C:31]2[CH2:36][CH2:35][CH:34]([NH:37][C:38](=[O:44])[O:39][C:40]([CH3:43])([CH3:42])[CH3:41])[CH2:33][CH:32]=2)O1.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:31]3[CH2:36][CH2:35][CH:34]([NH:37][C:38](=[O:44])[O:39][C:40]([CH3:43])([CH3:42])[CH3:41])[CH2:33][CH:32]=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 66570714tert-butyl N-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-en-1-yl]carbamateHCID 772308275-chloro-1-(cyclopropylmethyl)-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

Product 1

HCID 71128770tert-Butyl {4-[1-(2,2-dimethylpropyl)-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl]cyclohex-3-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) (410 mg, 1.616 mmol), Cs2CO3 (1.14 g, 3.50 mmol), tert-butyl [4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-en-1-yl]carbamate (692 mg, 2.141 mmol), & bis(tri-t-butylphosphine)palladium(0) (183 mg, 0.358 mmol), followed by anhydrous 1,4-dioxane (2.5 mL) & water (0.5 mL). The reaction mixture was then heated to 100° C. for 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 tert-Butyl {4-[1-(2,2-dimethylpropyl)-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl]cyclohex-3-en-1-yl}carbamate (17-1) as a yellow solid/foam. HRMS m/z (M+H): calculated=415.2704; observed=415.2705

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-66a4a5e1747f4dbc9d8fe742fe336263
Source dataset
uspto-grants-2016_04
Patent number
US09315518B2

Reaction notes

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