Tetrahydrofuran → 3-[9-Chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]pentan-3-ol

HRID 1399044Notes

Reaction equation

HRID 1399044 reaction equation
[CH2:1]([Mg]Br)[CH3:2].[Cl:5][C:6]1[CH:7]=[CH:8][C:9]([C:27](OC)=[O:28])=[C:10]2[C:14]=1[N:13]=[C:12]1[N:15]([C:19]3[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:20]=3[Cl:26])[CH2:16][CH2:17][CH2:18][N:11]21.O1CC[CH2:33][CH2:32]1>>[Cl:5][C:6]1[C:14]2[N:13]=[C:12]3[N:15]([C:19]4[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:20]=4[Cl:26])[CH2:16][CH2:17][CH2:18][N:11]3[C:10]=2[C:9]([C:27]([OH:28])([CH2:1][CH3:2])[CH2:32][CH3:33])=[CH:8][CH:7]=1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 57785909Methyl 9-chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylateHCID 178418443HCID 178418443, compound

Product 1

HCID 577863903-[9-Chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]pentan-3-olYield 49%

Conditions

Temperature
60 °C

Procedure

Ethylmagnesium bromide (3.0 M solution in diethyl ether, 2.9 mL, 8.7 mmol) was added to a stirred solution of methyl 9-chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylate (720 mg, 1.75 mmol) in tetrahydrofuran (7.0 mL), and the mixture was stirred at 60° C. for 2 hr. The reaction was quenched by water, and the mixture was 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 10-50% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the solid, which was recrystallized from ethanol to give the title compound as a colorless crystal (378 mg, 0.861 mmol, 49%).

Workup

  1. customThe reaction was quenched by water
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe combined organic layer was washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography on silica gel eluting with a 10-50% ethyl acetate/n-hexane gradient mixture
  8. concentrationThe filtrate was concentrated in vacuo
  9. customto give the solid, which
  10. customwas recrystallized from ethanol

Sources & evidence

ORD record
ord-0c8ed2f1a5394754a2a4deb5cde78152
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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