Tetrahydrofuran → HCID 57860321, compound

HRID 1947145Notes

Reaction equation

HRID 1947145 reaction equation
[CH3:1][O:2][C:3]1[C:7]2[C:8](=[O:25])[N:9]([CH2:16][C:17](=[O:24])[C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:15]=3[C:6]=2[N:5]([CH3:26])[C:4]=1[C:27]([NH:29][CH:30]1[CH2:34][CH2:33][NH:32][CH2:31]1)=[O:28].C(N(CC)CC)C.C1COCC1.C([O:50][CH2:51][C:52](Cl)=[O:53])(=O)C>C(OCC)(=O)C>[OH:53][CH2:52][C:51]([N:32]1[CH2:33][CH2:34][CH:30]([NH:29][C:27]([C:4]2[N:5]([CH3:26])[C:6]3[C:15]4[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=4[N:9]([CH2:16][C:17](=[O:24])[C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[C:8](=[O:25])[C:7]=3[C:3]=2[O:2][CH3:1])=[O:28])[CH2:31]1)=[O:50]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 26297Acetoxyacetyl chlorideHCID 57860345HCID 57860345, compound

Product 1

HCID 57860321HCID 57860321, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of the thus-obtained 3-methoxy-1-methyl-4-oxo-5-(2-oxo-2-phenylethyl)-N-pyrrolidin-3-yl-4,5-dihydro-1H-pyrrolo[3,2-c]quinoline-2-carboxamide (153 mg, 0.327 mmol), triethylamine (99.7 μL, 0.720 mmol) and THF (3 mL) was added acetoxyacetyl chloride (38.7 μL, 0.360 mmol) at 0° C., and the mixture was stirred at room temperature for 15 hr. The reaction mixture was diluted with ethyl acetate, washed with water and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by aminosilica gel chromatography (eluate; ethyl acetate). The obtained oil was dissolved in THF (4 mL) and ethanol (12 mL), 8N aqueous sodium hydroxide solution (1 mL) was added and the mixture was stirred at room temperature for 1.5 hr. The reaction mixture was diluted with water, acidified with 1N hydrochloric acid (8.5 mL), and extracted twice with ethyl acetate. The extract was combined, washed with saturated brine, dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by aminosilica gel chromatography (eluate; ethyl acetate/methanol=10/0-9/1). Recrystallization of the obtained solid from ethyl acetate-THF gave the title compound (121 mg, 72%) as a white powder.

Workup

  1. washwashed with water and saturated brine
  2. dry with materialdried over magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by aminosilica gel chromatography (eluate; ethyl acetate)
  5. dissolutionThe obtained oil was dissolved in THF (4 mL)
  6. additionethanol (12 mL), 8N aqueous sodium hydroxide solution (1 mL) was added
  7. stirringthe mixture was stirred at room temperature for 1.5 hr
  8. additionThe reaction mixture was diluted with water
  9. extractionextracted twice with ethyl acetate
  10. washwashed with saturated brine
  11. dry with materialdried over magnesium sulfate
  12. concentrationconcentrated under reduced pressure
  13. customThe residue was purified by aminosilica gel chromatography (eluate; ethyl acetate/methanol=10/0-9/1)
  14. customRecrystallization of the obtained solid from ethyl acetate-THF

Sources & evidence

ORD record
ord-0994dca6c5bf49a9acbabdf2c2322fca
Source dataset
uspto-grants-2013_03
Patent number
US08399449B2

Reaction notes

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