Cesium carbonate → 6-(6-benzyloxypyrid-2-yl)-N-phenylimidazo[1,2-a]pyridine-2-carboxamide

HRID 1878465Notes

Reaction equation

HRID 1878465 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11](Br)[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br.[C:23]1([NH:29][C:30]([C:32]2[N:33]=[C:34]3[CH:39]=[CH:38][C:37](B4OC(C)(C)C(C)(C)O4)=[CH:36][N:35]3[CH:49]=2)=[O:31])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>O1CCOCC1.O.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]>[CH2:1]([O:8][C:9]1[N:10]=[C:11]([C:37]2[CH:38]=[CH:39][C:34]3[N:35]([CH:49]=[C:32]([C:30]([NH:29][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[O:31])[N:33]=3)[CH:36]=2)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 8174752-Benzyloxy-6-bromopyridineHCID 68778296N-phenyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2-a]pyridine-2-carboxamide hydrobromide

Product 1

HCID 687800626-(6-benzyloxypyrid-2-yl)-N-phenylimidazo[1,2-a]pyridine-2-carboxamideYield 75.4%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
110 °C

Procedure

To a solution of 250 mg of 2-benzyloxy-6-bromopyridine in 12 mL of dioxane are added a solution of 1.234 g of caesium carbonate in 3 mL of water, 34.6 mg of [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium and then 546 mg of N-phenyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2-a]pyridine-2-carboxamide hydrobromide (1:1). The mixture is heated at 110° C. for 2 hours 45 minutes, and then cooled and filtered. The solid is washed with a small amount of methanol and then with dichloromethane and is then taken up in 250 mL of boiling methanol containing 5 mL of trifluoroacetic acid. The insoluble matter is filtered off and washed with methanol and then with dichloromethane and the filtrate is concentrated to dryness under reduced pressure. The residue is chromatographed on a silica cartridge, eluting with a gradient of from 0 to 5% of methanol in dichloromethane. The fractions containing the pure expected product are combined and concentrated to dryness under reduced pressure to give 0.3 g of 6-(6-benzyloxypyrid-2-yl)-N-phenylimidazo[1,2-a]pyridine-2-carboxamide in the form of a white solid.

Workup

  1. temperaturecooled
  2. filtrationfiltered
  3. washThe solid is washed with a small amount of methanol
  4. filtrationThe insoluble matter is filtered off
  5. washwashed with methanol
  6. concentrationwith dichloromethane and the filtrate is concentrated to dryness under reduced pressure
  7. customThe residue is chromatographed on a silica cartridge
  8. washeluting with a gradient of from 0 to 5% of methanol in dichloromethane
  9. additionThe fractions containing the pure expected product
  10. concentrationconcentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-d1bf7e8e4f9446158d05e6beac7d5997
Source dataset
uspto-grants-2012_11
Patent number
US08314109B2

Reaction notes

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