N-Iodosuccinimide → tert-butyl 6-amino-7-iodo-1-methyl-1H-imidazo[4,5-c]pyridin-4-yl(2,4-dimethoxybenzyl)carbamate

HRID 220342Notes

Reaction equation

HRID 220342 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[CH:3]=1.[I:31]N1C(=O)CCC1=O>CC#N>[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]([CH3:12])([CH3:13])[CH3:14])[C:5]2[N:27]=[CH:28][N:29]([CH3:30])[C:4]=2[C:3]=1[I:31]

Participants

4

Reactant 2

HCID 120273N-IodosuccinimideHCID 58180570Tert-butyl 2,4-dimethoxybenzyl6-amino-1-methyl-1h-imidazo[4,5-c]pyridin-4-ylcarbamate

Product 1

HCID 58180507tert-butyl 6-amino-7-iodo-1-methyl-1H-imidazo[4,5-c]pyridin-4-yl(2,4-dimethoxybenzyl)carbamateYield 82%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
0 °C

Procedure

In a round bottom flask, tert-butyl 6-amino-1-methyl-1H-imidazo[4,5-c]pyridin-4-yl(2,4-dimethoxybenzyl)carbamate (example 1D, 7.887 g, 19.08 mmol) was dissolved in MeCN (200 mL) and cooled to 0° C. N-Iodosuccinimide (4.51 g, 20.03 mmol) was dissolved in the remaining MeCN (50 mL) and added dropwise to the reaction mixture over 40 min. The reaction mixture was stirred at 0° C. for an additional 10 min and was quenched with 2 M sodium hydrogensulfite (125 mL). Stirring and temperature were maintained for 50 min. The mixture was transferred to a separatory funnel. The aqueous layer was extracted with CH2Cl2 (3×100 mL). The combined organic layers were washed with water and brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude residue was purified by flash chromatography using an Isco 120 g column eluting with 20-100% ethyl acetate/CH2Cl2 to provide tert-butyl 6-amino-7-iodo-1-methyl-1H-imidazo[4,5-c]pyridin-4-yl(2,4-dimethoxybenzyl)carbamate (8.436 g, 82% yield) as a pale yellow solid.

Workup

  1. additionadded dropwise to the reaction mixture over 40 min
  2. customwas quenched with 2 M sodium hydrogensulfite (125 mL)
  3. stirringStirring
  4. temperaturetemperature were maintained for 50 min
  5. customThe mixture was transferred to a separatory funnel
  6. extractionThe aqueous layer was extracted with CH2Cl2 (3×100 mL)
  7. washThe combined organic layers were washed with water and brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude residue was purified by flash chromatography
  12. washeluting with 20-100% ethyl acetate/CH2Cl2

Sources & evidence

ORD record
ord-93a6d4527c544ad8ab0bf1ae6d3a8739
Source dataset
uspto-grants-2012_06
Patent number
US08202881B2

Reaction notes

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