Acetic Anhydride → 1-[1-(4-Acetyl-2-chlorophenyl)-9-chloro-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]propyl acetate

HRID 1399158Notes

Reaction equation

HRID 1399158 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:26](=[O:28])[CH3:27])[CH:5]=[CH:6][C:7]=1[N:8]1[C:13]2=[N:14][C:15]3[C:20]([Cl:21])=[CH:19][CH:18]=[C:17]([CH:22]([OH:25])[CH2:23][CH3:24])[C:16]=3[N:12]2[CH2:11][CH2:10][CH2:9]1.[O:29]1CC[CH2:31][CH2:30]1.C(OC(=O)C)(=O)C>N1C=CC=CC=1>[C:30]([O:25][CH:22]([C:17]1[C:16]2[N:12]3[CH2:11][CH2:10][CH2:9][N:8]([C:7]4[CH:6]=[CH:5][C:4]([C:26](=[O:28])[CH3:27])=[CH:3][C:2]=4[Cl:1])[C:13]3=[N:14][C:15]=2[C:20]([Cl:21])=[CH:19][CH:18]=1)[CH2:23][CH3:24])(=[O:29])[CH3:31]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 8028TetrahydrofuranHCID 577862331-{3-Chloro-4-[9-chloro-6-(1-hydroxypropyl)-3,4-dihydropyrimido[1,2-a]benzimidazol-1(2H)-yl]phenyl}ethanone

Product 1

HCID 577858981-[1-(4-Acetyl-2-chlorophenyl)-9-chloro-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]propyl acetateYield 70%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of 1-{3-Chloro-4-[9-chloro-6-(1-hydroxypropyl)-3,4-dihydropyrimido[1,2-a]benzimidazol-1(2H)-yl]phenyl}ethanone (120.0 mg, 0.287 mmol) in pyridine (0.2 mL)/tetrahydrofuran (0.5 mL) was added acetic anhydride (0.5 mL) at 0° C. The reaction mixture was stirred at room temperature for 7 hrs. The mixture was concentrated. The residue was neutralized with aqueous saturated sodium hydrogen carbonate and extracted with ethyl acetate (×3). The combined organic layer was washed with brine (×1), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with a 10-40% ethyl acetate/n-hexane gradient mixture. The residue was recrystallized from ethanol/n-hexane to give the title compound as a colorless powder (92.5 mg, 0.201 mmol, 70%).

Workup

  1. concentrationThe mixture was concentrated
  2. extractionextracted with ethyl acetate (×3)
  3. washThe combined organic layer was washed with brine (×1)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel column chromatography
  8. washeluting with a 10-40% ethyl acetate/n-hexane gradient mixture
  9. customThe residue was recrystallized from ethanol/n-hexane

Sources & evidence

ORD record
ord-6700dbf14ef448cbb187690c09b86993
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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