Sodium hydride → HCID 18375789, compound

HRID 2268967Notes

Reaction equation

HRID 2268967 reaction equation
[H-].[Na+].[CH3:3][N:4]([O:16][CH3:17])[C:5]([C:7]1[CH:15]=[CH:14][C:10]2[N:11]=[CH:12][NH:13][C:9]=2[CH:8]=1)=[O:6].[CH3:18][S:19][C:20]1[N:25]=[C:24](Cl)[CH:23]=[CH:22][N:21]=1>CN(C=O)C>[CH3:18][S:19][C:20]1[N:25]=[C:24]([N:11]2[C:10]3[CH:14]=[CH:15][C:7]([C:5]([N:4]([CH3:3])[O:16][CH3:17])=[O:6])=[CH:8][C:9]=3[N:13]=[CH:12]2)[CH:23]=[CH:22][N:21]=1.[CH3:18][S:19][C:20]1[N:25]=[C:24]([N:13]2[C:9]3[CH:8]=[C:7]([C:5]([N:4]([CH3:3])[O:16][CH3:17])=[O:6])[CH:15]=[CH:14][C:10]=3[N:11]=[CH:12]2)[CH:23]=[CH:22][N:21]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 971134-Chloro-2-methylthiopyrimidineHCID 18375839HCID 18375839, compound

Product 2

HCID 18375789HCID 18375789, compoundHCID 18375864HCID 18375864, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
100 °C

Procedure

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, 5.5 Hz, 1H); 3.6 (s, 3H); 3.42 (s, 3H); 2.68 (s, 3H).

Workup

  1. customThe ice bath was removed
  2. custom(10 min)
  3. temperaturethen cooled down to 0° C.
  4. customquenched with H2O carefully
  5. additionThe reaction mixture was poured in to a separatory funnel
  6. extractionextracted with EtOAc
  7. washThe combined extracts were washed with H2O
  8. dry with materialdried over Na2SO4
  9. customThe crude material was purified by flash chromatography (1:200 crude material: silica gel)

Sources & evidence

ORD record
ord-a3f54c32a00f486f9d5f9682c84dc86c
Source dataset
uspto-grants-2001_12
Patent number
US06329380B1

Reaction notes

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