Cesium carbonate → (1-{4-[7-(3-Methyl-ureido)-3-phenyl-imidazo[1,2-a]pyridin-2-yl]-phenyl}-cyclobutyl)-carbamic acid tert-butyl ester

HRID 872334Notes

Reaction equation

HRID 872334 reaction equation
[C:1]([O:5][C:6](=[O:34])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[N:19]=[C:20]4[CH:25]=[C:24](Br)[CH:23]=[CH:22][N:21]4[C:27]=3[C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:41][NH:42][C:43]([NH2:45])=[O:44]>O1CCOCC1.CN(C=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>[C:1]([O:5][C:6](=[O:34])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[N:19]=[C:20]4[CH:25]=[C:24]([NH:45][C:43]([NH:42][CH3:41])=[O:44])[CH:23]=[CH:22][N:21]4[C:27]=3[C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 11719MethylureaHCID 66665545{1-[4-(7-Bromo-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester

Product 1

HCID 66666180(1-{4-[7-(3-Methyl-ureido)-3-phenyl-imidazo[1,2-a]pyridin-2-yl]-phenyl}-cyclobutyl)-carbamic acid tert-butyl esterYield 101.3%

Reagents, catalysts & solvents 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of {1-[4-(7-bromo-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (100 mg, 0.193 mmol), Pd2 dba3 (3.6 mg, 0.004 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (7 mg, 0.012 mmol), cesium carbonate (75 mg, 0.231 mmol) and methylurea (74 mg, 1.0 mmol) in dioxane (2.3 mL) and DMF (0.8 mL) was degassed, placed under an argon atmosphere and heated at 110° C. for 5 hours. On cooling, the reaction was partitioned between aqueous sodium hydrogen carbonate solution and DCM and the organic phase washed with brine, dried and concentrated in vacuo to give the crude title compound (100 mg) which was used in the next step without further purification.

Workup

  1. customwas degassed
  2. temperatureOn cooling
  3. customthe reaction was partitioned between aqueous sodium hydrogen carbonate solution and DCM
  4. washthe organic phase washed with brine
  5. customdried
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5e7df4a027f04ac48d799d66cceff823
Source dataset
uspto-grants-2015_03
Patent number
US08975265B2

Reaction notes

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