5-Aminobenzimidazole → HCID 15549643, compound

HRID 2268942Notes

Reaction equation

HRID 2268942 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][C:5]2[N:6]=[CH:7][NH:8][C:4]=2[CH:3]=1.[H-].[Na+].[CH3:13][S:14][C:15]1[N:20]=[C:19](Cl)[CH:18]=[CH:17][N:16]=1>CN(C=O)C>[CH3:13][S:14][C:15]1[N:20]=[C:19]([N:8]2[C:4]3[CH:3]=[C:2]([NH2:1])[CH:10]=[CH:9][C:5]=3[N:6]=[CH:7]2)[CH:18]=[CH:17][N:16]=1.[CH3:13][S:14][C:15]1[N:20]=[C:19]([N:6]2[C:5]3[CH:9]=[CH:10][C:2]([NH2:1])=[CH:3][C:4]=3[N:8]=[CH:7]2)[CH:18]=[CH:17][N:16]=1

Participants

6

Reactant 3

HCID 136235-AminobenzimidazoleHCID 24758Sodium hydrideHCID 971134-Chloro-2-methylthiopyrimidine

Product 2

HCID 15549643HCID 15549643, compoundHCID 15549644HCID 15549644, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirred solution of 5-aminobenzimidazole (700 mg, 5.26 mmol, 1 eq) in DMF (21 mL) was added NaH (231 mg, 5.78 mmol, 1.1 eq, (60% suspension in oil)). The mixture was allowed to stir until gas evolution ceased. To the DMF solution was added 2-methylthio-4-chloropyrimidine (0.612 mL, 5.26 mmol, 1 eq) dropwise via syringe. The mixture was allowed to stir overnight. The DMF was removed under reduced pressure and the residue was diluted with water and extracted 3× with CH2Cl2. The organic extracts were combined, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The mixture was purified by preparative thin layer chromatography (eluted 2× with 3.5% MeOH/CH2Cl2) to give 149 mg 2-methylthio-4-[6-aminobenzimidazol-1-yl]pyrimidine (faster regioisomer) and 89 mg 2-methylthio-4-[5-aminobenzimidazol-1-yl]pyrimidine (slower regioisomer). 2-methylthio-4-[6-aminobenzimidazol-1-yl]pyrimidine (faster regioisomer): 1H NMR (500 MHz, CD3OD): δ 8.68 (1H, s); 8.58 (1H, d, J=5.5 Hz); 7.68 (1H, d, J=2 Hz); 7.45 (2H, m); 6.81 (1H, dd, J=2 Hz, J=8.5 Hz); 2.67 (3H, s). 2-methylthio-4-[5-aminobenzimidazol-1-yl]pyrimidine (slower regioisomer): 1H NMR (500 MHz, CD3OD): δ 8.81 (1H, s); 8.56 (1H, d, J=5.5 Hz); 8.11 (1H, d, J=8.5 Hz); 7.46 (1H, d, J=5.5 Hz); 7.04 (1H, d, J=2 Hz); 6.87 (1H, dd, J=2 Hz, J=8.5 Hz); 2.65 (3H, s).

Workup

  1. stirringto stir overnight
  2. customThe DMF was removed under reduced pressure
  3. additionthe residue was diluted with water
  4. extractionextracted 3× with CH2Cl2
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe mixture was purified by preparative thin layer chromatography (eluted 2× with 3.5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-0e46e8aa858f4c9694dbc9ccf534ee1e
Source dataset
uspto-grants-2001_12
Patent number
US06329380B1

Reaction notes

Loading…