Hydrochloric Acid → 4-amino-1-benzyl-6-(1H-imidazol-2-yl)-3H-imidazo[4,5-c]pyridin-2-one

HRID 639609Notes

Reaction equation

HRID 639609 reaction equation
C([O:3][C:4](=O)[N:5]([C:13]1[CH:18]=[C:17]([C:19]2[N:20](COCC[Si](C)(C)C)[CH:21]=[CH:22][N:23]=2)[N:16]=[C:15]([NH2:32])[C:14]=1[N+:33]([O-])=O)[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)C.N1C=CN=C1.Cl>[Ni].C(O)(=O)C.O1CCOCC1>[NH2:32][C:15]1[C:14]2[NH:33][C:4](=[O:3])[N:5]([CH2:6][C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=3)[C:13]=2[CH:18]=[C:17]([C:19]2[NH:20][CH:21]=[CH:22][N:23]=2)[N:16]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 795ImidazoleHCID 67456488{2-amino-3-nitro-6-[1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-pyridin-4-yl}-benzyl-carbamic acid ethyl ester

Product 1

HCID 497716534-amino-1-benzyl-6-(1H-imidazol-2-yl)-3H-imidazo[4,5-c]pyridin-2-oneYield 26.9%

Reagents, catalysts & solvents 3

HCID 935NickelCatalystHCID 176Acetic AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

The title compound was prepared following the method of Example 20 using {2-amino-3-nitro-6-[1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-pyridin-4-yl}-benzyl-carbamic acid ethyl ester (174 mg) and Raney nickel (5 mg) in acetic acid (3 ml). This gave initially the SEM protected imidazole compound. Hydrogen chloride in dioxane (4 M, 1 ml) was then added drop-wise and the solution left to stir at room temperature for 24 hours. The reaction mixture was then transferred to a microwave vial (Biotage, 2-5 ml) and heated under microwave irradiation for 10 minutes at 110° C. (Biotage, Initiator 8). The reaction mixture was evaporated then re-dissolved in methanol and the solution loaded onto a cation-exchange cartridge (Bakerbond, sulphonic acid bonded-phase, 1 g). The cartridge was washed with methanol (2×5 ml) to remove impurities and then the product released by eluting with ammonia in methanol (2 M, 5 ml). The desired fractions were combined and evaporated to a brown solid. This was triturated with isopropanol and the solid collected by filtration then washed with more isopropanol, providing the title compound (28 mg) as a pale brown solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 5.02 (s, 2 H) 5.58 (s, 2 H) 6.91 (s, 1 H) 7.06 (s, 1 H) 7.11 (s, 1 H) 7.25-7.36 (m, 5 H) 10.53 (s, 1 H) 11.99 (s, 1 H). LCMS Rt=1.52 m/z 307 [MH]+hm

Workup

  1. customThe title compound was prepared
  2. customThis gave initially the SEM
  3. waitthe solution left
  4. customThe reaction mixture was evaporated
  5. dissolutionthen re-dissolved in methanol
  6. washThe cartridge was washed with methanol (2×5 ml)
  7. customto remove impurities
  8. washby eluting with ammonia in methanol (2 M, 5 ml)
  9. customevaporated to a brown solid
  10. customThis was triturated with isopropanol
  11. filtrationthe solid collected by filtration
  12. washthen washed with more isopropanol

Sources & evidence

ORD record
ord-f0bc26f3ebee4d1e9a71a3ebf4e6659f
Source dataset
uspto-grants-2010_04
Patent number
US07691877B2

Reaction notes

Loading…