Iodoethane → 3-[4-(benzyloxy)phenyl]-6-chloro-1-ethyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

HRID 1429978

Reaction equation

HRID 1429978 reaction equation
Cl[C:2]1[C:7]([NH:8][C:9](=[O:15])OC(C)(C)C)=[CH:6][C:5]([Cl:16])=[CH:4][N:3]=1.[CH2:17]([O:24][C:25]1[CH:31]=[CH:30][C:28]([NH2:29])=[CH:27][CH:26]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[CH3:32][C:33]1(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.CC(C)([O-])C.[Na+].[H-].[Na+].C(I)C.[Cl-].[Cl-].[Ca+2]>C1(C)C=CC=CC=1.CN(C=O)C.CO.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].CC(O)C>[CH2:17]([O:24][C:25]1[CH:26]=[CH:27][C:28]([N:29]2[C:2]3=[N:3][CH:4]=[C:5]([Cl:16])[CH:6]=[C:7]3[N:8]([CH2:32][CH3:33])[C:9]2=[O:15])=[CH:30][CH:31]=1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

13

Reactant 7

HCID 6340IodoethaneHCID 228604-BenzyloxyanilineHCID 24758Sodium hydrideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 5284359Calcium ChlorideHCID 23676156Sodium t-butoxideHCID 86660673Tert-butyl 2,5-dichloropyridin-3-ylcarbamate

Product 1

HCID 585773703-[4-(benzyloxy)phenyl]-6-chloro-1-ethyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-oneYield 247.5%

Reagents, catalysts & solvents 5

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 887MethanolSolventHCID 1140TolueneSolventHCID 3776IsopropanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

The mixture of tert-butyl (2,5-dichloropyridin-3-yl)carbamate (7.0 g), 4-(benzyloxy)aniline (7.95 g), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (1.231 g), Pd2(dba)3 (0.974 g) and sodium tert-butoxide (3.58 g) in toluene (160 mL)-2-propanol (40.0 mL) was stirred at 100° C. under Ar overnight. The reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (silica gel, eluted with 0%-100% EtOAc in hexane) to give intermediate. To the intermediate in DMF (100 mL) were added NaH (3.19 g) and ethyl iodide (20.75 g). The mixture was stirred at room temperature under a dry atmosphere (CaCl2 tube) for 1 h. The reaction mixture was diluted with MeOH and concentrated in vacuo. The residue was purified by column chromatography (NH silica gel, eluted with 0%-50% EtOAc in hexane) to give 3-[4-(benzyloxy)phenyl]-6-chloro-1-ethyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (2 g) as a colorless solid.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customThe residue was purified by column chromatography (silica gel, eluted with 0%-100% EtOAc in hexane)
  3. customto give intermediate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography (NH silica gel, eluted with 0%-50% EtOAc in hexane)

Sources & evidence

ORD record
ord-c2ab3139321147b69361ff6e1bc9e353
Source dataset
uspto-grants-2015_01
Patent number
US08940758B2

Linked notes

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