Dimethylformamide → Ethyl 6-(3-Hydroxy-1-propynyl)-1-methyl-4-oxo-1,4-dihydro[1,5]naphthyridine-3-carboxylate

HRID 411239Notes

Reaction equation

HRID 411239 reaction equation
C(N(CC)CC)C.[CH2:8]([OH:11])[C:9]#[CH:10].Cl[C:13]1[N:14]=[C:15]2[C:20](=[CH:21][CH:22]=1)[N:19]([CH3:23])[CH:18]=[C:17]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[C:16]2=[O:29].CN(C=O)C>CCOCC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[OH:11][CH2:8][C:9]#[C:10][C:13]1[N:14]=[C:15]2[C:20](=[CH:21][CH:22]=1)[N:19]([CH3:23])[CH:18]=[C:17]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[C:16]2=[O:29]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 7859Propargyl alcohol2×HCID 8471TriethylamineHCID 22397136Ethyl 6-Chloro-1-methyl-4-oxo-1,4-dihydro[1,5]naphthyridine-3-carboxylate

Product 1

HCID 22397164Ethyl 6-(3-Hydroxy-1-propynyl)-1-methyl-4-oxo-1,4-dihydro[1,5]naphthyridine-3-carboxylateYield 55%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

Triethylamine (10 mL) is added to dry cuprous iodide (52 mg) under nitrogen. The mixture is stirred for 5 minutes and propargyl alcohol (50 μL) is added. After stirring another 5 minutes, dichlorobis(triphenylphosphine)palladium(II) (48 mg) is added. The mixture is again stirred for 5 minutes before the addition of ethyl 6-chloro-1-methyl-4-oxo-1,4-dihydro[1,5]naphthyridine-3-carboxylate (Preparation 59, 367 mg) and DMF (10 mL). After stirring another 5 minutes, the remaining propargyl alcohol (660 μL) is added, and the reaction is tightly capped and stirred at 70° C. for 11 hours. After cooling, the dark mixture is diluted with ether (75 mL), sonicated to break up the solids, and filtered. The collected solid is washed with ether and dried under vacuum. The crude solid is recrystallized from 95% ethanol (100 mL, dissolved at reflux with the addition of a few drops of water, then cooled to 0° C. overnight), affording 219 mg (55%) of the title compound as a beige solid. Physical characteristics. 1H NMR (DMSO-d6) δ 8.68, 8.21, 7.85, 5.5, 4.38, 4.23, 3.90, 1.29; HRMS (FAB) (C15H14N2O4+H) m/z 287.1035. Anal. Found (C15H14N2O4.0.12 H2O): C, 62.48; H, 5.00; N, 9.62.

Workup

  1. stirringAfter stirring another 5 minutes
  2. stirringAfter stirring another 5 minutes
  3. customthe reaction is tightly capped
  4. stirringstirred at 70° C. for 11 hours
  5. temperatureAfter cooling
  6. customsonicated
  7. filtrationfiltered
  8. washThe collected solid is washed with ether
  9. customdried under vacuum
  10. customThe crude solid is recrystallized from 95% ethanol (100 mL
  11. dissolutiondissolved
  12. temperatureat reflux with the addition of a few drops of water

Sources & evidence

ORD record
ord-5c3b5e341cff490fb3b64915435b8283
Source dataset
uspto-grants-2003_05
Patent number
US06559145B2

Reaction notes

Loading…