Diisopropylethylamine → HCID 90314144, compound

HRID 1505812Notes

Reaction equation

HRID 1505812 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:14]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[C:19]([Cl:24])[CH:18]=2)=[O:15])[C:5]2[N:9]=[C:8]([N:10]([CH3:12])[CH3:11])[NH:7][C:6]=2[CH:13]=1.C(N(CC)C(C)C)(C)C.[Cl:34][C:35]1[CH:43]=[CH:42][CH:41]=[C:40]([F:44])[C:36]=1[C:37](Cl)=[O:38]>C1COCC1.C(OCC)(=O)C>[Cl:34][C:35]1[CH:43]=[CH:42][CH:41]=[C:40]([F:44])[C:36]=1[C:37]([NH:1][C:2]1[CH:3]=[C:4]([C:14]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[C:19]([Cl:24])[CH:18]=2)=[O:15])[C:5]2[N:9]=[C:8]([N:10]([CH3:11])[CH3:12])[NH:7][C:6]=2[CH:13]=1)=[O:38]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 27365472-Chloro-6-fluorobenzoyl chlorideHCID 90229246HCID 90229246, compound

Product 1

HCID 90314144HCID 90314144, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 6-amino-N-(3-chloro-4-methylphenyl)-2-(dimethylamino)-1H-benzimidazole-4-carboxamide (50 mg) in THF (1.5 mL), was added N,N-diisopropylethylamine (37 μL) and the mixture was stirred under ice-cooling. To the mixture was added slowly 2-chloro-6-fluorobenzoyl chloride (24 μL), and it was stirred for 2 hours. The reaction mixture was diluted with ethyl acetate, washed sequentially with saturated aqueous sodium bicarbonate and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified on column chromatography to obtain 6-{[(2-chloro-6-fluorophenyl)carbonyl]amino}-N-(3-chloro-4-methylphenyl)-2-(dimethylamino)-1H-benzimidazole-4-carboxamide (30 mg) as pale yellow powder. This was then suspended in MeOH (1 mL), 2N hydrogen chloride/MeOH (1 Eq) was added to obtain a homogeneous solution, and MeOH was removed under reduced pressure. The residue was triturated in n-hexane/ethyl acetate (1:1), and the precipitate was collected by filtration and dried to obtain the titled compound (24 mg) as pale purple powder.

Workup

  1. temperaturecooling
  2. stirringwas stirred for 2 hours
  3. washwashed sequentially with saturated aqueous sodium bicarbonate and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified on column chromatography

Sources & evidence

ORD record
ord-2584032c068b49099859f75b54366613
Source dataset
uspto-grants-2015_12
Patent number
US09216968B2

Reaction notes

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