Triethylamine → methyl 4-chloro-2-[(2,4-dichloro-6-methylphenyl)amino]-1-(2-hydroxyethyl)-1H-benzimidazole-7-carboxylate

HRID 1398922Notes

Reaction equation

HRID 1398922 reaction equation
[NH2:1][C:2]1[C:3]([NH:13][CH2:14][CH2:15][OH:16])=[C:4]([CH:9]=[CH:10][C:11]=1[Cl:12])[C:5]([O:7][CH3:8])=[O:6].[Cl:17][C:18]1[CH:23]=[C:22]([Cl:24])[CH:21]=[C:20]([CH3:25])[C:19]=1[N:26]=[C:27]=S.Cl.C(N=C=NCCCN(C)C)C.C(N(CC)CC)C>O1CCCC1.O>[Cl:12][C:11]1[C:2]2[N:1]=[C:27]([NH:26][C:19]3[C:20]([CH3:25])=[CH:21][C:22]([Cl:24])=[CH:23][C:18]=3[Cl:17])[N:13]([CH2:14][CH2:15][OH:16])[C:3]=2[C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:9][CH:10]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27360131,5-Dichloro-2-isothiocyanato-3-methylbenzene2×HCID 68738315Methyl 3-amino-4-chloro-2-[(2-hydroxyethyl)amino]benzoate

Product 1

HCID 68762627methyl 4-chloro-2-[(2,4-dichloro-6-methylphenyl)amino]-1-(2-hydroxyethyl)-1H-benzimidazole-7-carboxylateYield 30.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

A solution of methyl 3-amino-4-chloro-2-[(2-hydroxyethyl)amino]benzoate (290 mg, 1.19 mmol) and 2,4-dichloro-6-methylphenylisothiocyanate (284.4 mg, 1.3 mmol) in tetrahydrofuran (12 mL) was stirred at 45° C. for 62 hr. The mixture was warmed to 60° C. and stirred at, 60° C. for 24 hr. 2,4-Dichloro-6-methylphenylisothiocyanate (104 mg, 0.48 mmol) was added to the reaction mixture and the mixture was stirred at 60° C. for 26 hr. Water was added to the reaction mixture at room temperature and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on NH-silica gel eluting with a 50-100% ethyl acetate/n-hexane gradient mixture give a red amorphous (261.4 mg). To a mixture of the amorphous (261.4 mg) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (119 mg, 0.62 mmol) in tetrahydrofuran (11.2 mL) was added triethylamine (0.0866 mL, 0.62 mmol) at room temperature. The mixture was stirred at 50° C. for 16 hr. Water was added to the reaction mixture at room temperature and the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to give the title compound (156.3 mg, 0.36 mmol, 30%) as a pale yellow solid.

Workup

  1. stirringthe mixture was stirred at 60° C. for 26 hr
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography on NH-silica gel eluting with a 50-100% ethyl acetate/n-hexane gradient mixture
  7. customgive a red amorphous (261.4 mg)
  8. stirringThe mixture was stirred at 50° C. for 16 hr
  9. extractionthe mixture was extracted with ethyl acetate
  10. washThe organic layer was washed with water and brine
  11. dry with materialdried over anhydrous magnesium sulfate
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-63d00751170141eab59b80e3f20a87e2
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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