1,1'-Carbonyldiimidazole → HCID 67024450, compound

HRID 389138Notes

Reaction equation

HRID 389138 reaction equation
C1N=CN(C(N2C=NC=C2)=O)C=1.[Cl:13][C:14]1[CH:15]=[CH:16][C:17]([O:23][C:24]([CH3:42])([C:26]2[N:30]([CH3:31])[C:29]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=3[C:38]([F:41])([F:40])[F:39])=[N:28][N:27]=2)[CH3:25])=[C:18]([CH:22]=1)[C:19]([OH:21])=O.C1CCN2C(=NCCC2)CC1.[CH3:54][S:55]([NH2:58])(=[O:57])=[O:56]>CN(C=O)C.O>[ClH:13].[Cl:13][C:14]1[CH:15]=[CH:16][C:17]([O:23][C:24]([CH3:25])([C:26]2[N:30]([CH3:31])[C:29]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=3[C:38]([F:41])([F:39])[F:40])=[N:28][N:27]=2)[CH3:42])=[C:18]([CH:22]=1)[C:19]([NH:58][S:55]([CH3:54])(=[O:57])=[O:56])=[O:21]

Participants

7

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 72879MethanesulfonamideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 58244031HCID 58244031, compound

Product 1

HCID 67024450HCID 67024450, compoundYield 76.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

CDI (180 mg) was added to a solution of 5-chloro-2-(1-methyl-1-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}ethoxy)benzoic acid (300 mg) in DMF, followed by stirring at 50° C. for one hour. DBU (325 mg) and methanesulfonamide (200 mg) were added to the reaction solution, followed by stirring at 50° C. for 1.5 hours. Water was added to the reaction solution, followed by extraction with ethyl acetate three times, with chloroform once and then with chloroform-methanol (4:1) mixed solution twice. The combined organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=9:1), ethyl acetate (3 ml) and methanol (1.5 ml) were added to the resulting amorphous, and a 4M hydrogen chloride-ethyl acetate solution (150 μl) was added thereto. The solvent was evaporated under reduced pressure and was powdered with diisopropylether to obtain, as a colorless solid, 5-chloro-2-(1-methyl-1-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}ethoxy)-N-(methylsulfonyl)benzamide monohydrochloride (143.8 mg).

Workup

  1. stirringby stirring at 50° C. for 1.5 hours
  2. extractionfollowed by extraction with ethyl acetate three times, with chloroform once
  3. additionwith chloroform-methanol (4:1) mixed solution twice
  4. washThe combined organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was then evaporated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (ethyl acetate:methanol=9:1), ethyl acetate (3 ml) and methanol (1.5 ml)
  8. additionwere added to the resulting amorphous, and a 4M hydrogen chloride-ethyl acetate solution (150 μl)
  9. additionwas added
  10. customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-8b7014a9de06486bad897899225de6ca
Source dataset
uspto-grants-2013_02
Patent number
US08377923B2

Reaction notes

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