Methylamine → 1-(2,4-Dichlorophenyl)-N,N-dimethyl-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxamide

HRID 1399025Notes

Reaction equation

HRID 1399025 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:14]2=[N:15][C:16]3[C:17](=[C:18]([C:22]([OH:24])=O)[CH:19]=[CH:20][CH:21]=3)[N:13]2[CH2:12][CH2:11][CH2:10]1.ON1C2C=CC=CC=2N=N1.Cl.[CH2:36]([N:38]=[C:39]=NCCCN(C)C)C.CN>CN(C)C=O.C(=O)([O-])O.[Na+]>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:14]2=[N:15][C:16]3[C:17](=[C:18]([C:22]([N:38]([CH3:39])[CH3:36])=[O:24])[CH:19]=[CH:20][CH:21]=3)[N:13]2[CH2:12][CH2:11][CH2:10]1

Participants

7

Reactant 4

HCID 6329MethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 577864031-(2,4-Dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylic acid

Product 1

HCID 577859611-(2,4-Dichlorophenyl)-N,N-dimethyl-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxamideYield 66.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a suspension of 1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylic acid (430 mg, 1.18 mmol) in N,N-dimethylformamide (8.0 mL) were added 1-hydroxy-1H-benzotriazole (235 mg, 1.53 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (249 mg, 1.30 mmol), and methylamine (2.0 M solution in tetrahydrofuran, 1.20 mL, 2.40 mmol). The mixture was stirred at room temperature for 15 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 40-85% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the solid, which was recrystallized from ethanol/ethyl acetate to give the title compound as a colorless crystal (305 mg, 0.783 mmol, 66%).

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 40-85% ethyl acetate/n-hexane gradient mixture
  7. concentrationThe filtrate was concentrated in vacuo
  8. customto give the solid, which
  9. customwas recrystallized from ethanol/ethyl acetate

Sources & evidence

ORD record
ord-53ece8ad73344e36b895dc876ba68874
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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