Ethanol → HCID 11154740, compound

HRID 2181621Notes

Reaction equation

HRID 2181621 reaction equation
[CH2:1]([O:8][CH2:9][N:10]1[C:18]2[C:17](=[O:19])[N:16](C)[C:15](=O)[N:14]([C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:23]=3[Cl:29])[C:13]=2[N:12]=[C:11]1[CH2:30][CH3:31])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCO.[OH-].[Na+].C([O-])(O)=O.[Na+]>O1CCOCC1>[CH2:1]([O:8][CH2:9][N:10]1[C:18]([C:17]([NH:16][CH3:15])=[O:19])=[C:13]([NH:14][C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:23]=2[Cl:29])[N:12]=[C:11]1[CH2:30][CH3:31])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 702EthanolHCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 10151688HCID 10151688, compound

Product 1

HCID 11154740HCID 11154740, compoundYield 59.1%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

7-benzyloxymethyl-3-(2,4-dichlorophenyl)-8-ethyl-1-methyl-3,7-dihydro-1H-purine-2,6-dione (5.20 g, 11.32 mmol) was dissolved in dioxane (25 mL) and the mixture was treated with EtOH (25 mL) and aqueous NaOH (50 mL, 3 N). The reaction mixture was heated at 60° C. for 2 h. The mixture was then cooled to rt and was transferred to a separatory funnel containing saturated aqueous NaHCO3 (100 mL). The aqueous layer was extracted with EtOAc (3×100 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel (40% ethyl acetate in hexanes→40% ethyl acetate in hexanes with 0.2% MeOH) to afford 1-benzyloxymethyl-4-[(2,4-dichlorophenyl)amino]-2-ethyl-N-methyl-1H-imidazole-5-carboxamide (2.90 g, 59% yield) as a light yellow amorphous solid: 1H NMR (300 MHz, CDCl3) δ 9.35 (s, 1H), 8.41 (d, J=8.8 Hz, 1H), 7.44-7.29 (m, 7H), 7.16 (dd, J=9.1, 2.5 Hz, 1H), 5.45 (s, 2H), 4.63 (s, 2H), 2.89 (d, J=4.8 Hz, 3H); 2.65 (q, J=7.7 Hz, 2H), 1.35 (t, J=7.7 Hz, 3H); LRMS (APCI) m/e 433.1 [(M+H)+, calcd for C21H23N4O2Cl2 433.1].

Workup

  1. temperatureThe mixture was then cooled to rt
  2. customwas transferred to a separatory funnel
  3. extractionThe aqueous layer was extracted with EtOAc (3×100 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography on silica gel (40% ethyl acetate in hexanes→40% ethyl acetate in hexanes with 0.2% MeOH)

Sources & evidence

ORD record
ord-151eace157fd4bcd81fb4016906b97e6
Source dataset
uspto-grants-2005_05
Patent number
US06894045B2

Reaction notes

Loading…