Tetrahydrofuran → 1-{3-Chloro-4-[9-chloro-6-(1-hydroxypropyl)-3,4-dihydropyrimido[1,2-a]benzimidazol-1(2H)-yl]phenyl}ethanone

HRID 1628807Notes

Reaction equation

HRID 1628807 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)=[CH:17][C:16]=4[Cl:22])[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5](C(O)CC)=[CH:4][CH:3]=1.C([Li])CCC.CN(C)[C:34](=[O:36])[CH3:35].[O:38]1[CH2:42][CH2:41][CH2:40]C1>>[Cl:1][C:2]1[CH:3]=[C:4]([C:34](=[O:36])[CH3:35])[CH:5]=[CH:6][C:10]=1[N:9]1[C:8]2=[N:11][C:15]3[C:16]([Cl:22])=[CH:17][CH:18]=[C:19]([CH:42]([OH:38])[CH2:41][CH3:40])[C:20]=3[N:7]2[CH2:14][CH2:13][CH2:12]1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 31374DimethylacetamideHCID 44156374HCID 44156374, compoundHCID 178418339Butyllithium

Product 1

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

Procedure

To a solution of 1-[9-chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]propan-1-ol (700.0 mg, 1.538 mmol) in tetrahydrofuran (12.0 mL) was added n-butyllithium (1.60 M solution in n-hexane, 2.57 mL, 4.12 mmol) at −78° C., and the mixture was stirred for 30 min. To the mixture was added N,N-dimethylacetamide (0.77 mL, 8.24 mmol) at −78° C. The mixture was stirred at room temperature for 3 hrs. The mixture was quenched with aqueous saturated ammonium chloride and extracted with ethyl acetate (×3). The combined organic layer was washed with water (×2) and brine (×1), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with a 0-100% ethyl acetate/n-hexane gradient mixture to give the title compound as a pale yellow amorphous (130.2 mg, 0.311 mmol, 20%).

Workup

  1. stirringThe mixture was stirred at room temperature for 3 hrs
  2. customThe mixture was quenched with aqueous saturated ammonium chloride
  3. extractionextracted with ethyl acetate (×3)
  4. washThe combined organic layer was washed with water (×2) and brine (×1)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel column chromatography
  9. washeluting with a 0-100% ethyl acetate/n-hexane gradient mixture

Sources & evidence

ORD record
ord-9d09073ecc664fc9bdc94db41c49a0f0
Source dataset
uspto-grants-2014_07
Patent number
US08785460B2

Reaction notes

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