1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → tert-butyl 5-(2-oxo-1,2-dihydro-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-indole-1-carboxylate

HRID 1429905Notes

Reaction equation

HRID 1429905 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:6][CH2:5]2.Cl[C:19]1[C:24]([NH:25][C:26](=O)[O:27]C(C)(C)C)=[CH:23][CH:22]=[CH:21][N:20]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CC(C)([O-])C.[Na+]>CC(O)C.C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[O:27]=[C:26]1[N:1]([C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[N:7]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:6][CH2:5]3)[C:19]2=[N:20][CH:21]=[CH:22][CH:23]=[C:24]2[NH:25]1

Participants

9

Reactant 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 11961738tert-Butyl (2-chloropyridin-3-yl)carbamateHCID 22240520tert-Butyl 5-amino-2,3-dihydro-1H-indole-1-carboxylateHCID 23676156Sodium t-butoxide

Product 1

HCID 58577557tert-butyl 5-(2-oxo-1,2-dihydro-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-indole-1-carboxylateYield 26.6%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of tert-butyl 5-amino-2,3-dihydro-1H-indole-1-carboxylate (4.10 g), tert-butyl 2-chloropyridin-3-ylcarbamate (4.20 g), Pd2(dba)3 (0.48 g), Xantphos (0.608 g), sodium tert-butoxide (2.52 g) in 2-propanol (64 mL) and toluene (12 mL) was stirred at 90° C. for 40 h, and treated with water and extracted with EtOAc. The organic layer was dried over MgSO4 and concentrated in vacuo. The residue was suspended in CH3CN and the precipitate was collected by filtration to give tert-butyl 5-(2-oxo-1,2-dihydro-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-indole-1-carboxylate (1.64 g). The filtrate was evaporated and then the residue was chromatographed on silica gel eluting with AcOEt/Hexane=2/1 to afford second crop (1.4 g).

Workup

  1. extractionextracted with EtOAc
  2. dry with materialThe organic layer was dried over MgSO4
  3. concentrationconcentrated in vacuo
  4. filtrationthe precipitate was collected by filtration

Sources & evidence

ORD record
ord-e3d89f6c67e14846916a06406aebd1d9
Source dataset
uspto-grants-2015_01
Patent number
US08940758B2

Reaction notes

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