Cesium carbonate → tert-butyl 2,4-dimethoxybenzyl(6-(diphenylmethyleneamino)-1-methyl-1H-imidazo[4,5-c]pyridin-4-yl)carbamate

HRID 220340Notes

Reaction equation

HRID 220340 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][C:18]=2[O:25][CH3:26])[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[C:5]2[N:27]=[CH:28][N:29]([CH3:30])[C:4]=2[CH:3]=1.[C:31](=[NH:44])([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>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].O1CCOCC1>[CH3:26][O:25][C:18]1[CH:19]=[C:20]([O:23][CH3:24])[CH:21]=[CH:22][C:17]=1[CH2:16][N:8]([C:6]1[C:5]2[N:27]=[CH:28][N:29]([CH3:30])[C:4]=2[CH:3]=[C:2]([N:44]=[C:31]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[N:7]=1)[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 136809Benzophenone imineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 58180538tert-butyl 6-chloro-1-methyl-1H-imidazo[4,5-c]pyridin-4-yl(2,4-dimethoxybenzyl)carbamate

Product 1

HCID 58180611tert-butyl 2,4-dimethoxybenzyl(6-(diphenylmethyleneamino)-1-methyl-1H-imidazo[4,5-c]pyridin-4-yl)carbamateYield 89%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

Anhydrous dioxane (4 mL) was added to a mixture of tert-butyl 6-chloro-1-methyl-1H-imidazo[4,5-c]pyridin-4-yl(2,4-dimethoxybenzyl)carbamate (example 1B, 0.638 g, 1.474 mmol), benzophenone imine (0.297 mL, 1.769 mmol), Pd2(dba)3 (0.270 g, 0.295 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.256 g, 0.442 mmol), and cesium carbonate (0.672 g, 2.063 mmol). The reaction mixture was heated to 90° C. overnight. After cooling to rt, solvent was removed in vacuo. The residue was partitioned between ethyl acetate and water. The organic layer was washed twice with water, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The crude residue was purified by flash chromatography using an Isco 40 g column eluting with 50-100% ethyl acetate/hexane to provide tert-butyl 2,4-dimethoxybenzyl(6-(diphenylmethyleneamino)-1-methyl-1H-imidazo[4,5-c]pyridin-4-yl)carbamate (0.757 g, 89% yield) as a light yellow solid.

Workup

  1. temperatureAfter cooling to rt
  2. customsolvent was removed in vacuo
  3. customThe residue was partitioned between ethyl acetate and water
  4. washThe organic layer was washed twice with water
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude residue was purified by flash chromatography
  9. washeluting with 50-100% ethyl acetate/hexane

Sources & evidence

ORD record
ord-932d3f86af01455f9e11a0b025a57147
Source dataset
uspto-grants-2012_06
Patent number
US08202881B2

Reaction notes

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