Pyridine → (Z)-1-[9-chloro-1-(2,4-dichlorophenyl)-3,4-dihydro-2H-pyrimido[1,2-a]benzimidazol-6-yl]-N-ethoxypropan-1-imine

HRID 1628703Notes

Reaction equation

HRID 1628703 reaction equation
[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:15]4[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=4[Cl:22])[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([C:23](=O)[CH2:24][CH3:25])=[CH:4][CH:3]=1.Cl.[CH2:28]([O:30][NH2:31])[CH3:29].N1C=CC=CC=1>C(O)C>[CH2:28]([O:30]/[N:31]=[C:23](\[C:5]1[C:6]2[N:7]3[CH2:14][CH2:13][CH2:12][N:11]([C:15]4[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=4[Cl:22])[C:8]3=[N:9][C:10]=2[C:2]([Cl:1])=[CH:3][CH:4]=1)/[CH2:24][CH3:25])[CH3:29]

Participants

5

Reactant 3

HCID 1049PyridineHCID 76850O-ethylhydroxylamine hydrochlorideHCID 577863001-[9-Chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]propan-1-one

Product 1

HCID 57786268(Z)-1-[9-chloro-1-(2,4-dichlorophenyl)-3,4-dihydro-2H-pyrimido[1,2-a]benzimidazol-6-yl]-N-ethoxypropan-1-imine

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 1-[9-chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]propan-1-one (250 mg, 0.612 mmol), O-ethylhydroxylamine hydrochloride (179 mg, 1.84 mmol) and pyridine (1.5 mL) in ethanol (6.0 mL) was stirred at 80° C. for 26 hr. The mixture was concentrated in vacuo, 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 20-40% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the solid, which was recrystallized from ethyl acetate/diisopropyl ether to give the title compounds as a colorless crystal respectively (E (Example 123): 111 mg, 0.246 mmol, 40%, Z (Example 124): 31.0 mg, 0.0686 mmol, 11%).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. additiondiluted with saturated aqueous sodium hydrogen carbonate
  3. extractionextracted with ethyl acetate
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash column chromatography on silica gel eluting with a 20-40% ethyl acetate/n-hexane gradient mixture
  9. concentrationThe filtrate was concentrated in vacuo
  10. customto give the solid, which
  11. customwas recrystallized from ethyl acetate/diisopropyl ether

Sources & evidence

ORD record
ord-e0bb53ea10114d06babf5afce2a99f51
Source dataset
uspto-grants-2014_07
Patent number
US08785460B2

Reaction notes

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