Dimethylformamide → N-(4-Chlorobenzyl)-2-(hydroxymethyl)-8-(3-hydroxy-1-propynyl)-6-oxo-1,2-dihydro-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxamide

HRID 1168504Notes

Reaction equation

HRID 1168504 reaction equation
[Cl:1][C:2]1[CH:27]=[CH:26][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:19](=[O:20])[C:18]3[C:13]4=[C:14]([CH2:22][CH:23]([CH2:24][OH:25])[N:12]4[CH:11]=2)[CH:15]=[C:16](I)[CH:17]=3)=[O:9])=[CH:4][CH:3]=1.CN([CH:31]=[O:32])C.[CH2:33](N(CC)CC)[CH3:34]>>[Cl:1][C:2]1[CH:27]=[CH:26][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:19](=[O:20])[C:18]3[C:13]4=[C:14]([CH2:22][CH:23]([CH2:24][OH:25])[N:12]4[CH:11]=2)[CH:15]=[C:16]([C:33]#[C:34][CH2:31][OH:32])[CH:17]=3)=[O:9])=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 12083028N-(4-Chlorobenzyl)-2-(hydroxymethyl)-8-iodo-6-oxo-1,2-dihydro-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxamide

Product 1

HCID 10137080N-(4-Chlorobenzyl)-2-(hydroxymethyl)-8-(3-hydroxy-1-propynyl)-6-oxo-1,2-dihydro-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxamideYield 70%

Conditions

Temperature
65 °C

Procedure

A solution containing N-(4-chlorobenzyl)-2-(hydroxymethyl)-8-iodo-6-oxo-1,2-dihydro-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxamide (Preparation 10, 0.15 g), anhydrous DMF (6 mL), and triethylamine (0.8 mL) is purged with nitrogen three times before adding propargyl alcohol (19 μL), copper(I)iodide (14 mg), and PdCl2(PPh3)2 (8 mg). The solution is heated to 65° C. and then is cooled, diluted with CH2Cl2 (25 mL), and poured into water (30 mL). The organic layer is washed with brine, dried (Na2SO4), filtered, and concentrated to give a brown residue. The crude product is chromatographed eluting with 0-6% methanol in CH2Cl2 (250 mL each) to give 90 mg (70%) of the title compound as a white solid. Physical characteristics: M.p. 224-225° C.; MS (ESI+) m/z 423 (M+H)+.

Workup

  1. customis purged with nitrogen three times
  2. additionbefore adding propargyl alcohol (19 μL), copper(I)iodide (14 mg), and PdCl2(PPh3)2 (8 mg)
  3. temperatureis cooled
  4. additiondiluted with CH2Cl2 (25 mL)
  5. additionpoured into water (30 mL)
  6. washThe organic layer is washed with brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give a brown residue
  11. customThe crude product is chromatographed
  12. washeluting with 0-6% methanol in CH2Cl2 (250 mL each)

Sources & evidence

ORD record
ord-807d7addab5341a382779e66cf53d1cb
Source dataset
uspto-grants-2003_09
Patent number
US06624159B2

Reaction notes

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