Ethyl pyruvate → Ethyl 4-(tert-butoxycarbonyl(2,4-dimethoxybenzyl)amino)-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxylate

HRID 220343Notes

Reaction equation

HRID 220343 reaction equation
[NH2:1][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[C:3]=1I.[C:32]([O:37][CH2:38][CH3:39])(=[O:36])[C:33]([CH3:35])=O.CN(C1CCCCC1)C1CCCCC1>CC(N(C)C)=O.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]>[C:11]([O:10][C:9]([N:8]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][C:18]=1[O:25][CH3:26])[C:6]1[N:7]=[C:2]2[NH:1][C:33]([C:32]([O:37][CH2:38][CH3:39])=[O:36])=[CH:35][C:3]2=[C:4]2[N:29]([CH3:30])[CH:28]=[N:27][C:5]=12)=[O:15])([CH3:14])([CH3:13])[CH3:12]

Participants

6

Reactant 3

HCID 12041Ethyl pyruvateHCID 24210N-Methyl dicyclohexylamineHCID 58180507tert-butyl 6-amino-7-iodo-1-methyl-1H-imidazo[4,5-c]pyridin-4-yl(2,4-dimethoxybenzyl)carbamate

Product 1

HCID 69809714Ethyl 4-(tert-butoxycarbonyl(2,4-dimethoxybenzyl)amino)-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxylateYield 86%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
60 °C

Procedure

To a flask charged with tert-butyl 6-amino-7-iodo-1-methyl-1H-imidazo[4,5-c]pyridin-4-yl(2,4-dimethoxybenzyl)carbamate (example 1E, 3.49 g, 6.47 mmol) in DMA (43.1 mL) was added Pd2(dba)3 (0.474 g, 0.518 mmol), ethyl pyruvate (7.22 mL, 64.7 mmol), and N-methyldicyclohexylamine (2.77 mL, 12.94 mmol). The reaction mixture was sparged with argon for 10 min and heated at 60° C. 6 h. The reaction was complete by LCMS. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate and saturated aqueous NaHCO3. The resultant emulsion was vacuum filtered through a pad of Celite and transferred to a separatory funnel. The aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with 10% aqueous LiCl solution (2×). The organic phase was dried over MgSO4, filtered and concentrated in vacuo. The brown residue was purified by flash chromatography using an Isco 120 g column eluting with 40-80% ethyl acetate/hexane to yield ethyl 4-(tert-butoxycarbonyl(2,4-dimethoxybenzyl)amino)-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxylate (2.830 g, 86% yield)

Workup

  1. customThe reaction mixture was sparged with argon for 10 min
  2. custom6 h
  3. temperatureAfter cooling to room temperature
  4. additionthe reaction mixture was diluted with ethyl acetate and saturated aqueous NaHCO3
  5. filtrationfiltered through a pad of Celite
  6. customtransferred to a separatory funnel
  7. extractionThe aqueous layer was extracted with ethyl acetate
  8. washThe combined organic layers were washed with 10% aqueous LiCl solution (2×)
  9. dry with materialThe organic phase was dried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe brown residue was purified by flash chromatography
  13. washeluting with 40-80% ethyl acetate/hexane

Sources & evidence

ORD record
ord-36d2765394594b9c8f768f6874763a84
Source dataset
uspto-grants-2012_06
Patent number
US08202881B2

Reaction notes

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