Sodium hydride → HCID 18375789, compound

Participants

Reaction Conditions

Reaction Steps

To a suspension of NaH (210 mg, 60% suspension in oil, 5.21 mmol) in DMF (10 mL) at 0° C. was added 5-(N-methyl-N-methoxyaminocarbonyl)benzimidazole (890 mg, 4.34 mmol) dissolved in DMF (10 mL) dropwise. The ice bath was removed, and the reaction mixture was stirred until the mixture became homogeneous (10 min) then added 2-methylthio-4-chloropyrimidine (610 μL, 5.21 mmol). The mixture was heated at 100° C. for 1.5 h then cooled down to 0° C. and quenched with H2O carefully. The reaction mixture was poured in to a separatory funnel and extracted with EtOAc. The combined extracts were washed with H2O followed by brine and dried over Na2SO4. The crude material was purified by flash chromatography (1:200 crude material:silica gel) using 1% MeOH/EtOAc system to obtain 516 mg of 2-methylthio-4-[5-(N-methyl-N-methoxyaminocarbonyl)-benzimidazol-1-yl]pyrimidine and 429 mg of 2-methylthio-4-[6-(N-methyl-N-methoxyaminocarbonyl)benzimidazol-1-yl]pyrimidine. 2-methylthio-4-[5-(N-methyl-N-methoxyaminocarbonyl)-benzimidazol-1-yl]pyrimidine: Partial 1H NMR (500 MHz, CDCl3): δ 8.71 (s, 1H); 8.65 (d, J=5.5 Hz, 1H); 8.25 (s, 1H); 8.24 (d, J=8.5 Hz, 1H); 7.82 (d, J=5.5 Hz, 1H); 7.22 (d, J=5.5 Hz, 1H); 3.58 (s, 3H); 3.42 (s, 3H); 2.68 (s, 3H). 2-methylthio-4-[6-(N-methyl-N-methoxyaminocarbonyl)-benzimidazol-1-yl]pyrimidine: Partial 1H NMR (500 MHz, CDCl3): δ 8.75 (s, 1H); 8.64 (d, J=5.5 Hz, 1H); 8.63 (s, 1H); 7.87 (d, J=8.5 Hz, 1H); 7.77 (d, J=8.5 Hz, 1H); 7.23 (d, J=5.5 Hz, 1H); 3.6 (s, 3H); 3.42 (s, 3H); 2.68 (s, 3H).

Provenance & Evidence