Water → HCID 178521272, compound

HRID 235934Notes

Reaction equation

HRID 235934 reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[NH:11][CH:12]=[C:13]([C:15]3[S:16][CH:17]=[CH:18][CH:19]=3)[N:14]=2)=[CH:6][CH:5]=1.S(C1C=[CH:29][C:27](C)=[CH:26]C=1)([O-])(=O)=O.[OH2:31]>CN(C)C=O>[CH:27]1([NH:11][CH2:10][CH:7]([OH:31])[CH2:6][O:3][C:4]2[CH:5]=[CH:6][C:7]([C:10]3[NH:11][CH:12]=[C:13]([C:15]4[S:16][CH:17]=[CH:18][CH:19]=4)[N:14]=3)=[CH:8][CH:9]=2)[CH2:26][CH2:29]1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 85570p-ToluenesulfonateHCID 178515900HCID 178515900, compound

Product 1

HCID 178521272HCID 178521272, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

A solution of IV (6.80 g., 0.031 m) in pyridine (12 ml) is cooled to 10° C. and p-toluenesulfonyl chloride (5.91 g., 0.031 m) is added over 30 minutes, keeping temperature below 25° C. After stirring at 25° C. for 3 hours, a cold solution of K2CO3 (4.28 g., 0.031 m) in H2O (28 ml) is added and the mixture is extracted with CHCl3 (3×50 ml). The extracts are washed with H2O, dried and concentrated under reduced pressure below 50° C., initially using water aspiration and finally high vacuum to yield the tosylate a (11.27 g, 97%). Sodium hydride (1.39 g, 0.029 m, 50% dispersion in mineral oil) is added to a solution of 2-(p-hydroxyphenyl)-4-(2-thienyl)imidazole (7.00 g, 0.029 m) in dimethylformamide (50 ml) under nitrogen and the mixture is heated at 60° C. for 30 minutes. A solution of the tosylate (11.27 g, 0.030 m) in dimethylformamide (45 ml) is added and the mixture is refluxed for 16 hours. The reaction mixture is poured into H2O (300 ml) and extracted with ether (3×150 ml). The combined organic layers are extracted with cold 1N HCl (3×75 ml) and the acid layer added to sodium acetate (18.5 g, 0.23 m) and stirred at 25° C. for 5 hours. The solution is extracted with ether (2×), basified with saturated Na2CO3 solution, extracted with 10% MeOH-CHCl3 (3×150 ml), dried and concentrated under reduced pressure. The residue is chromatographed on silica gel and eluted with 5% MeOH-CHCl3 saturated with NH3. The product VII is crystallized from CH3CN (0.43 g., mp 169°-171.5° C.).

Workup

  1. temperaturethe mixture is refluxed for 16 hours
  2. extractionextracted with ether (3×150 ml)
  3. extractionThe combined organic layers are extracted with cold 1N HCl (3×75 ml)
  4. additionthe acid layer added to sodium acetate (18.5 g, 0.23 m)
  5. extractionThe solution is extracted with ether (2×)
  6. extractionextracted with 10% MeOH-CHCl3 (3×150 ml)
  7. customdried
  8. concentrationconcentrated under reduced pressure
  9. customThe residue is chromatographed on silica gel
  10. washeluted with 5% MeOH-CHCl3 saturated with NH3
  11. customThe product VII is crystallized from CH3CN (0.43 g., mp 169°-171.5° C.)

Sources & evidence

ORD record
ord-6875a47d36834c9789158741f0a743ec
Source dataset
uspto-grants-1987_02
Patent number
US04642311

Reaction notes

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