Aniline → HCID 178488982, compound

HRID 1067398Notes

Reaction equation

HRID 1067398 reaction equation
[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([C:15]3[NH:16][CH:17]=[C:18]([C:20](O)=[O:21])[N:19]=3)[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:5][CH2:4][CH2:3][CH2:2]1.O=S(Cl)Cl.[CH3:27][C:28]1[CH:34]=[CH:33][CH:32]=[C:31]([CH3:35])[C:29]=1[NH2:30].NC1C=CC=CC=1.[H-].[Na+]>CN(C=O)C.C1COCC1.Cl>[CH3:27][C:28]1[CH:34]=[CH:33][CH:32]=[C:31]([CH3:35])[C:29]=1[NH:30][C:20]([C:18]1[N:19]=[C:15]([C:9]2[CH:10]=[CH:11][C:12]([O:13][CH3:14])=[C:7]([O:6][CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5]3)[CH:8]=2)[NH:16][CH:17]=1)=[O:21]

Participants

9

Reactant 5

HCID 6115AnilineHCID 68962,6-DimethylanilineHCID 24386Thionyl ChlorideHCID 24758Sodium hydrideHCID 178488985HCID 178488985, compound

Product 1

HCID 178488982HCID 178488982, compoundYield 15%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

A mixture of 2-(3-cyclopentyloxy-4-methoxyphenyl)-imidazole-4-carboxylic acid (400 mg, 1.32 mmol) and SOCl2 (10 ml) containing DMF (1 drop) was heated to reflux for 2 hours. The volatiles were removed in vacuo and to the residue was added toluene (25 ml) and the solvent evaporated. This procedure was repeated to remove dissolved gaseous by-products. The residue was dissolved in THF (10 ml) and added dropwise at 0° C. over 10 minutes, to a solution of the salt of 2,6-dimethylaniline (510 μl, 4.14 mmol) in THF (30 ml) (formed by adding a solution of the aniline in THF (15 ml) to a suspension of NaH (167 mg, 4.14 mmol) is THF (15 ml) at room temperature). The resultant solution was stirred at room temperature for 48 hours, diluted with iN HCl (20 ml) and the mixture extracted with methylene chloride (2×50 ml). The combined organics were dried over Na2SO4 and the volatiles removed in vacuo. Flash chromatography (SiO2; CH2Cl2:EtOH (97:3)) afforded 2-(3-cyclopentyloxy-4-methoxyphenyl)-imidazole-4-carboxylic acid-2,6-dimethylphenyl amide (80 mg, 15%) as a pale yellow solid, mp 118-122° C.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 2 hours
  3. customThe volatiles were removed in vacuo and to the residue
  4. additionwas added toluene (25 ml)
  5. customthe solvent evaporated
  6. customto remove
  7. dissolutiondissolved gaseous by-products
  8. dissolutionThe residue was dissolved in THF (10 ml)
  9. customformed
  10. customat room temperature
  11. extractionthe mixture extracted with methylene chloride (2×50 ml)
  12. dry with materialThe combined organics were dried over Na2SO4
  13. customthe volatiles removed in vacuo

Sources & evidence

ORD record
ord-c58f90663f064023819c2571525bd25b
Source dataset
uspto-grants-2001_06
Patent number
US06248769B1

Reaction notes

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