Benzimidazole → HCID 86758759, compound

HRID 2300837Notes

Reaction equation

HRID 2300837 reaction equation
[H-].[Na+].[N:3]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[NH:5][CH:4]=1.[C:12]1([C@@H:18]([NH:20][C:21]2[N:26]=[C:25](Cl)[CH:24]=[C:23]([Cl:28])[N:22]=2)[CH3:19])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>CN(C=O)C>[C:12]1([C@@H:18]([NH:20][C:21]2[N:26]=[C:25]([N:3]3[C:7]4[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=4[N:5]=[CH:4]3)[CH:24]=[C:23]([Cl:28])[N:22]=2)[CH3:19])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

5

Reactant 3

HCID 5798BenzimidazoleHCID 24758Sodium hydrideHCID 86758758HCID 86758758, compound

Product 1

HCID 86758759HCID 86758759, compoundYield 61.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To a suspension of NaH (74 mg) in DMF (5 mL) at 0° C. was added benzimidazole (204 mg). The reaction mixture was stirred at 0° C. until gas evolution ceased, then stirred at room temperature until the mixture became homogeneous (ca. 10 min.). A solution of 2-[(S)-1-phenylethylamino]-4,6-dichloropyrimidine (412 mg) in DMF (2 mL) was added to the mixture, which was then placed in 100° C. oil bath for 1 h. The reaction mixture was cooled and carefully quenched with water. The layers were separated, and the aqueous layer was extracted CH2Cl2 (2×15 mL). Combined organic layers was washed with water and brine and dried over anhydrous Na2SO4. The solvent was concentrated under reduced pressure, and the crude product was purified by flash chromatography (1:5 EtOAc:hexanes) to give 330 mg of the title compound. 1H NMR (500 MHz, CDCl3): δ 8.21 (br s, 1H); 7.82 (d, J=7.5 Hz, 1H); 7.75 (br s, 1H); 7.45-7.28 (m, 7H); 6.8 (s, 1H); 5.92 (br s, 1H); 5.2 (br s, 1H); 1.62 (d, J=7.1 Hz, 3H). Mass spectrum (CI) 350.2 (M+1).

Workup

  1. stirringstirred at room temperature until the mixture
  2. custom(ca. 10 min.)
  3. customwas then placed in 100° C.
  4. customfor 1 h
  5. temperatureThe reaction mixture was cooled
  6. customcarefully quenched with water
  7. customThe layers were separated
  8. extractionthe aqueous layer was extracted CH2Cl2 (2×15 mL)
  9. washCombined organic layers was washed with water and brine
  10. dry with materialdried over anhydrous Na2SO4
  11. concentrationThe solvent was concentrated under reduced pressure
  12. customthe crude product was purified by flash chromatography (1:5 EtOAc:hexanes)

Sources & evidence

ORD record
ord-7851d649573a4d0c9b3376cff43a077e
Source dataset
uspto-grants-2002_12
Patent number
US06498165B1

Reaction notes

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