Acetone → HCID 86746536, compound

HRID 2081224Notes

Reaction equation

HRID 2081224 reaction equation
[F:1][C:2]1[C:10]2[NH:9][C:8]3[CH2:11][CH2:12][N:13]([CH2:16][C:17]4[N:18]=[CH:19][N:20](C(C5C=CC=CC=5)(C5C=CC=CC=5)C5C=CC=CC=5)[C:21]=4[CH3:22])[C:14](=[O:15])[C:7]=3[C:6]=2[CH:5]=[CH:4][CH:3]=1.[C:42](=[O:45])([O-:44])[O-].[K+].[K+].[CH2:48](Br)[C:49]#[CH:50].CC(C)=[O:54]>>[C:14]([OH:15])(=[O:54])/[CH:7]=[CH:8]\[C:42]([OH:44])=[O:45].[F:1][C:2]1[C:10]2[N:9]([CH2:50][C:49]#[CH:48])[C:8]3[CH2:11][CH2:12][N:13]([CH2:16][C:17]4[N:18]=[CH:19][NH:20][C:21]=4[CH3:22])[C:14](=[O:15])[C:7]=3[C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 4

HCID 180AcetoneHCID 7842Propargyl bromideHCID 11430Potassium CarbonateHCID 15712520HCID 15712520, compound

Product 1

HCID 86746536HCID 86746536, compound

Procedure

A stirred solution of 6-fluoro-2,3,4,5-tetrahydro-2-[[5-methyl-1-(triphenylmethyl) -1H-imidazol-4-yl]methyl]-1H-pyrido[4,3-b]indol-1-one (228 mg) in dry acetone (40 ml) and anhydrous potassium carbonate (116 mg) was treated with propargyl bromide (10% v/v solution in dry acetone; 1 ml) and heated at reflux overnight. After cooling, excess acetone was removed in vacuo, and the residue was partitioned between water (100 ml) and ethyl acetate (100 ml). The organic phase was washed with water (2×50 ml) and the combined aqueons extracts were washed with ethyl acetate (50 ml). The combined organic extracts were then concentrated in vacuo, and the residue was dissolved in a mixture of water (10 ml), glacial acetic acid (10 ml) and THF (15 ml) and heated to reflux for 2 h. The cooled solution was then basified with 2N sodium hydroxide (ca. 100 ml) and extracted with ethyl acetate (2×100 ml). The combined, dried organic extracts were adsorbed onto silica and purified by FCC eluting with System A (100:8:1) to give the free base of the title compound (95 mg). This was dissolved in the minimum hot dry methanol, and maleic acid (32 mg) was added. The solution was heated and then left to cool. Ether was added to precipitate the title compound (80 mg), m.p. 123°-124°.

Workup

  1. temperatureheated
  2. temperatureat reflux overnight
  3. temperatureAfter cooling
  4. customexcess acetone was removed in vacuo
  5. customthe residue was partitioned between water (100 ml) and ethyl acetate (100 ml)
  6. washThe organic phase was washed with water (2×50 ml)
  7. washthe combined aqueons extracts were washed with ethyl acetate (50 ml)
  8. concentrationThe combined organic extracts were then concentrated in vacuo
  9. dissolutionthe residue was dissolved in a mixture of water (10 ml), glacial acetic acid (10 ml) and THF (15 ml)
  10. temperatureheated
  11. temperatureto reflux for 2 h
  12. extractionextracted with ethyl acetate (2×100 ml)
  13. custompurified by FCC
  14. washeluting with System A (100:8:1)

Sources & evidence

ORD record
ord-c3722e777b264f7bb153a29a481dc47a
Source dataset
uspto-grants-1993_02
Patent number
US05183820

Reaction notes

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