Tetrahydrofuran → HCID 57786082, compound

HRID 1628883Notes

Reaction equation

HRID 1628883 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:24](OC)=[O:25])=[C:6]2[C:10]=1[N:9]=[C:8]1[N:11]([C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:16]=3[CH3:23])[CH2:12][CH2:13][CH2:14][N:7]21.[CH:28]1([Mg]Br)[CH2:30][CH2:29]1.O1[CH2:37][CH2:36][CH2:35]C1>>[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:15]4[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:16]=4[CH3:23])[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([C:24]([CH:35]2[CH2:36][CH2:37]2)([CH:28]2[CH2:30][CH2:29]2)[OH:25])=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 57786057HCID 57786057, compoundHCID 178418630HCID 178418630, compound

Product 1

HCID 57786082HCID 57786082, compoundYield 44%

Conditions

Temperature
70 °C

Procedure

Under nitrogen atmosphere, to a solution of methyl 9-chloro-1-(4-methoxy-2-methylphenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylate (0.10 g, 0.26 mmol) in tetrahydrofuran (1.3 mL) was added cyclopropyl magnesium bromide (1M solution in tetrahydrofuran, 1.3 mL, 1.30 mmol) at room temperature, and the mixture was stirred at 70° C. for 1 h. The reaction mixture was quenched by aqueous saturated ammonium chloride, 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 30% ethyl acetate/n-hexane mixture. The desired fractions were concentrated in vacuo. The residual oil was crystallized from ethyl acetate/n-hexane to give the title compound as a colorless crystal (50.1 mg, 0.11 mmol, 44%).

Workup

  1. customThe reaction mixture was quenched by aqueous saturated ammonium chloride
  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 30% ethyl acetate/n-hexane mixture
  8. concentrationThe desired fractions were concentrated in vacuo
  9. customThe residual oil was crystallized from ethyl acetate/n-hexane

Sources & evidence

ORD record
ord-8393df493657492383029a0b8b19985d
Source dataset
uspto-grants-2014_07
Patent number
US08785460B2

Reaction notes

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