Triethylamine → Methyl 4-chloro-2-{[6-(dimethylamino)-2-methylpyridin-3-yl]amino}-1-(3-hydroxypropyl)-1H-benzimidazole-7-carboxylate

HRID 1398845Notes

Reaction equation

HRID 1398845 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:21]([CH3:29])=[N:22][C:23]([N:26]([CH3:28])[CH3:27])=[CH:24][CH:25]=1.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:21]([CH3:29])=[N:22][C:23]([N:26]([CH3:28])[CH3:27])=[CH:24][CH:25]=3)[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 86632885Methyl 4-chloro-3-({[6-(dimethylamino)-2-methylpyridin-3-yl]carbamothioyl}amino)-2-[(3-hydroxypropyl)amino]benzoate

Product 1

HCID 68763664Methyl 4-chloro-2-{[6-(dimethylamino)-2-methylpyridin-3-yl]amino}-1-(3-hydroxypropyl)-1H-benzimidazole-7-carboxylateYield 50.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of the resulting thiourea (1.09 g), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (509 mg, 2.65 mmol), and triethylamine (0.37 mL) in tetrahydrofuran (10 mL) was stirred at 50° C. for 3 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 30-80% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the title compound as a colorless solid (510 mg, 1.22 mmol, 28% in 2 steps).

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 30-80% ethyl acetate/n-hexane gradient mixture
  7. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-4175cbe8543e4e69b8edb1c1d299bdcd
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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