Triethylamine → methyl 4-chloro-2-[(2,4-dichloro-6-methylphenyl)amino]-1-(3-hydroxypropyl)-1H-benzimidazole-7-carboxylate

HRID 1628715Notes

Reaction equation

HRID 1628715 reaction equation
[Cl:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([NH:12][CH2:13][CH2:14][CH2:15][OH:16])[C:3]=1[NH:17][C:18](=S)[NH:19][C:20]1[C:25]([CH3:26])=[CH:24][C:23]([Cl:27])=[CH:22][C:21]=1[Cl:28].Cl.C(N=C=NCCCN(C)C)C.C(N(CC)CC)C>O1CCCC1.C(=O)([O-])O.[Na+]>[Cl:1][C:2]1[C:3]2[N:17]=[C:18]([NH:19][C:20]3[C:25]([CH3:26])=[CH:24][C:23]([Cl:27])=[CH:22][C:21]=3[Cl:28])[N:12]([CH2:13][CH2:14][CH2:15][OH:16])[C:4]=2[C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:10][CH:11]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86632880Methyl 4-chloro-3-{[(2,4-dichloro-6-methylphenyl)carbamothioyl]amino}-2-[(3-hydroxypropyl)amino]benzoate

Product 1

HCID 68763420methyl 4-chloro-2-[(2,4-dichloro-6-methylphenyl)amino]-1-(3-hydroxypropyl)-1H-benzimidazole-7-carboxylate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of methyl 4-chloro-3-{[(2,4-dichloro-6-methylphenyl)carbamothioyl]amino}-2-[(3-hydroxypropyl)amino]benzoate (Reference example 118, 2.17 g, 4.55 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (872 mg, 4.55 mmol) and triethylamine (0.70 mL) in tetrahydrofuran (20 mL) was stirred at 50° C. for 12 hr. The mixture was diluted with saturated aqueous sodium hydrogen carbonate, and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with a 10-60% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give methyl 4-chloro-2-[(2,4-dichloro-6-methylphenyl)amino]-1-(3-hydroxypropyl)-1H-benzimidazole-7-carboxylate as a brown wax (1.67 g).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe combined organic layer was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash column chromatography on silica gel eluting with a 10-60% ethyl acetate/n-hexane gradient mixture
  7. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-6729c78608014e9f91cda87ef54332ba
Source dataset
uspto-grants-2014_07
Patent number
US08785460B2

Reaction notes

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