Propargyl alcohol → N-[(4-chlorophenyl)methyl]-6-(3-hydroxyprop-1-ynyl)-7-methoxy-1-methyl-4-oxo-1,8-naphthyridine-3-carboxamide

HRID 2120776Notes

Reaction equation

HRID 2120776 reaction equation
[Cl:1][C:2]1[CH:26]=[CH:25][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:19](=[O:20])[C:18]3[C:13](=[N:14][C:15]([O:22][CH3:23])=[C:16](I)[CH:17]=3)[N:12]([CH3:24])[CH:11]=2)=[O:9])=[CH:4][CH:3]=1.[CH2:27]([OH:30])[C:28]#[CH:29]>C(NCC)C.C1COCC1.C(Cl)Cl.[Cu](I)I.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>[Cl:1][C:2]1[CH:26]=[CH:25][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:19](=[O:20])[C:18]3[C:13](=[N:14][C:15]([O:22][CH3:23])=[C:16]([C:29]#[C:28][CH2:27][OH:30])[CH:17]=3)[N:12]([CH3:24])[CH:11]=2)=[O:9])=[CH:4][CH:3]=1

Participants

8

Reactant 2

HCID 7859Propargyl alcoholHCID 5276330N-[(4-chlorophenyl)methyl]-6-iodo-7-methoxy-1-methyl-4-oxo-1,8-naphthyridine-3-carboxamide

Product 1

HCID 5276332N-[(4-chlorophenyl)methyl]-6-(3-hydroxyprop-1-ynyl)-7-methoxy-1-methyl-4-oxo-1,8-naphthyridine-3-carboxamideYield 68%

Reagents, catalysts & solvents 5

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6344DichloromethaneSolventHCID 8021DiethylamineSolventHCID 8028TetrahydrofuranSolvent

Procedure

N-(4-chlorobenzyl)-6-iodo-7-methoxy-1-methyl-4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxamide (250 mg), copper iodide (40 mg) and dichlorobis(triphenylphosphine)palladium (30 mg) are dissolved in a mixture of diethylamine (15 mL) and THF (15 mL). To this is added propargyl alcohol (452 μL). The mixture is heated at reflux for 1 h, cooled to room temperature, diluted with CH2Cl2, washed with 1N HCl, brine, dried (MgSO4) and concentrated in vacuo. The residue is purified by silica gel chromatography (CH2Cl2/MeOH 1/0, 45/1, 19/1, 9/1) and the resulting product is recrystalized from MeOH to afford 144 mg (68%) of N-(4-chlorobenzyl)-6-(3-hydroxy-1-propynyl)-7-methoxy-1-methyl-4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxamide. Physical characteristics are as follows: 1H NMR (CDCl3) δ8.80, 8.60, 7.32, 4.65, 4.57, 4.13, 3.98; IR (diffuse reflectance) 2425, 2350, 2318, 2233, 1921, 1662, 1607, 1551, 1512, 1492, 1465, 1397, 1380, 1292, 809, cm−1; MS (El) m/z 411 (M+), 244, 86, 84, 80, 79, 78, 65, 63, 61, 51; HRMS (FAB) calcd for C21H18ClN3O4+H1 412.1064, found 412.1067.

Workup

  1. temperatureThe mixture is heated
  2. temperatureat reflux for 1 h
  3. washwashed with 1N HCl, brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified by silica gel chromatography (CH2Cl2/MeOH 1/0, 45/1, 19/1, 9/1)
  7. customthe resulting product is recrystalized from MeOH

Sources & evidence

ORD record
ord-6df4b4a7c7fb49a39353a2645d819aa1
Source dataset
uspto-grants-2004_02
Patent number
US06693114B2

Reaction notes

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