Diisopropylethylamine → 6-{[(2-bromo-6-fluorophenyl) carbonyl]amino}-N-(3-chloro-2-m ethylphenyl)-2-(methoxymethyl)-1H-benzimidazole-4-carboxamide

HRID 1505788Notes

Reaction equation

HRID 1505788 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:14]([NH:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:18]=2[CH3:24])=[O:15])[C:5]2[N:9]=[C:8]([CH2:10][O:11][CH3:12])[NH:7][C:6]=2[CH:13]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.[Br:58][C:59]1[CH:67]=[CH:66][CH:65]=[C:64]([F:68])[C:60]=1[C:61](O)=[O:62].C(=O)(O)[O-].[Na+]>CN(C=O)C>[Br:58][C:59]1[CH:67]=[CH:66][CH:65]=[C:64]([F:68])[C:60]=1[C:61]([NH:1][C:2]1[CH:3]=[C:4]([C:14]([NH:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:18]=2[CH3:24])=[O:15])[C:5]2[N:9]=[C:8]([CH2:10][O:11][CH3:12])[NH:7][C:6]=2[CH:13]=1)=[O:62]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 3026212-Bromo-6-fluorobenzoic acidHCID 516892Sodium BicarbonateHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 902293686-amino-N-(3-chloro-2-methylphenyl)-2-(methoxymethyl)-1H-benzimidazole-4-carboxamide

Product 1

HCID 715321486-{[(2-bromo-6-fluorophenyl) carbonyl]amino}-N-(3-chloro-2-m ethylphenyl)-2-(methoxymethyl)-1H-benzimidazole-4-carboxamideYield 58.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-amino-N-(3-chloro-2-methylphenyl)-2-(methoxymethyl)-1H-benzimidazole-4-carboxamide (50 mg) in DMF (1.5 mL), were added HBTU (66 mg), N,N-diisopropylethylamine (30 μL) and 2-bromo-6-fluorobenzoic acid (38 mg) in turn, and the mixture was stirred at room temperature for 24 hours. The reaction mixture was poured into saturated aqueous sodium bicarbonate, and extracted with ethyl acetate. The organic layer was separated, washed sequentially with water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified on column chromatography to obtain 6-{[(2-bromo-6-fluorophenyl) carbonyl]amino}-N-(3-chloro-2-m ethylphenyl)-2-(methoxymethyl)-1H-benzimidazole-4-carboxamide (46 mg). This was dissolved in ethyl acetate (2 mL), and treated with 4N hydrogen chloride/ethyl acetate (1.2 Eq). The precipitate was collected by filtration, and dried to obtain the titled compound (24 mg) as white powder.

Workup

  1. extractionextracted with ethyl acetate
  2. customThe organic layer was separated
  3. washwashed sequentially with water 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-4a731dc1f1b94665aec5fb6a9b6dd627
Source dataset
uspto-grants-2015_12
Patent number
US09216968B2

Reaction notes

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