Tetrahydrofuran → [9-Chloro-1-(4,6-dimethoxy-2-methylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl](dicyclopropyl)methanol

HRID 1628748Notes

Reaction equation

HRID 1628748 reaction equation
[CH:1]1([Mg]Br)[CH2:3][CH2:2]1.[Cl:6][C:7]1[CH:8]=[CH:9][C:10]([C:31]([O:33]C)=O)=[C:11]2[C:15]=1[N:14]=[C:13]1[N:16]([C:20]3[C:21]([O:29][CH3:30])=[N:22][C:23]([CH3:28])=[N:24][C:25]=3[O:26][CH3:27])[CH2:17][CH2:18][CH2:19][N:12]21.O1[CH2:39][CH2:38][CH2:37]C1>>[Cl:6][C:7]1[C:15]2[N:14]=[C:13]3[N:16]([C:20]4[C:25]([O:26][CH3:27])=[N:24][C:23]([CH3:28])=[N:22][C:21]=4[O:29][CH3:30])[CH2:17][CH2:18][CH2:19][N:12]3[C:11]=2[C:10]([C:31]([CH:37]2[CH2:38][CH2:39]2)([CH:1]2[CH2:3][CH2:2]2)[OH:33])=[CH:9][CH:8]=1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 57785929Methyl 9-chloro-1-(4,6-dimethoxy-2-methylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylateHCID 178418630HCID 178418630, compound

Product 1

HCID 57786189[9-Chloro-1-(4,6-dimethoxy-2-methylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl](dicyclopropyl)methanolYield 55%

Conditions

Temperature
50 °C

Procedure

Cyclopropylmagnesium bromide (1.0 M solution in tetrahydrofuran, 1.9 mL, 1.9 mmol) was added to a stirred solution of methyl 9-chloro-1-(4,6-dimethoxy-2-methylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylate (159 mg, 0.381 mmol) in tetrahydrofuran (3.8 mL), and the mixture was stirred at 50° C. for 11 hr. The reaction 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 15-50% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the solid, which was recrystallized from ethanol/ethyl acetate to give the title compound as a colorless crystal (98.6 mg, 0.210 mmol, 55%).

Workup

  1. customThe reaction 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 15-50% ethyl acetate/n-hexane gradient mixture
  8. concentrationThe filtrate was concentrated in vacuo
  9. customto give the solid, which
  10. customwas recrystallized from ethanol/ethyl acetate

Sources & evidence

ORD record
ord-079d1de69d074a5c873c7074f933a262
Source dataset
uspto-grants-2014_07
Patent number
US08785460B2

Reaction notes

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