Ethanol → Ethyl 6-[(4-chlorophenyl)methylcarbamoyl]-2-methoxy-8-methyl-5-oxo-1,8-naphthyridine-3-carboxylate

HRID 2120778Notes

Reaction equation

HRID 2120778 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.C1C=CC(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[CH2:56]([OH:58])[CH3:57].C(N(CC)CC)C.CN([CH:69]=[O:70])C>C(Cl)Cl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[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[CH:17]=[C:16]([C:69]([O:58][CH2:56][CH3:57])=[O:70])[C:15]([O:22][CH3:23])=[N:14][C:13]=3[N:12]([CH3:24])[CH:11]=2)=[O:9])=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 702EthanolHCID 6228DimethylformamideHCID 8471TriethylamineHCID 812191,3-Bis(diphenylphosphino)propaneHCID 5276330N-[(4-chlorophenyl)methyl]-6-iodo-7-methoxy-1-methyl-4-oxo-1,8-naphthyridine-3-carboxamide

Product 1

HCID 5276333Ethyl 6-[(4-chlorophenyl)methylcarbamoyl]-2-methoxy-8-methyl-5-oxo-1,8-naphthyridine-3-carboxylateYield 76%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

N-(4-Chlorobenzyl)-6-iodo-7-methoxy-1-methyl-4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxamide (700 mg), palladium acetate (32 mg), DPPP (60 mg), ethanol (10 mL) and triethylamine (1 mL) are dissolved in DMF (20 mL) in a steel bomb. The bomb is flushed with CO (3×) and then pressured with CO (400 psi) and the resulting reaction is stirred at 80° C. for 24 h, cooled to room temperature and diluted with CH2Cl2. The organic is washed with water, 1N HCl, brine, dried (MgSO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography (CH2Cl2/MeOH 1/0, 45/1) and then triturated with MeOH to afford 472 mg (76%) of ethyl 6-{[(4-chlorobenzyl)amino]carbonyl}-2-methoxy-8-methyl-5-oxo-5,8-dihydro[1,8]naphthyridine-3-carboxylate. Physical characteristics are as follows: 1H NMR (CDCl3) δ10.26-10.23, 9.18, 8.85, 7.32, 4.65, 4.40, 4.19, 4.00, 1.41; 13C NMR (CDCl3) δ176.33, 164.24, 163.76, 163.28, 150.17, 148.34, 142.24, 137.17, 132.94, 129.00, 128.73, 116.32, 113.96, 113.29, 61.57, 55.17, 42.86, 39.17, 14.24; IR (diffuse reflectance) 1965, 1727, 1663, 1609, 1568, 1542, 1514, 1493, 1466, 1390, 1297, 1260, 1141, 813, 799, cm−1; MS (EI) m/z 429 (M+), 431, 430, 429, 289, 263, 262, 261, 159, 140,77; Anal. calcd for C21H20ClN3O5: C, 58.68; H, 4.69; N. 9.77; Cl, 8.25. Found: C, 58.39; H, 4.70; N, 9.71.

Workup

  1. customThe bomb is flushed with CO (3×)
  2. customthe resulting reaction
  3. temperaturecooled to room temperature
  4. washThe organic is washed with water, 1N HCl, brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue is purified by silica gel chromatography (CH2Cl2/MeOH 1/0, 45/1)
  9. customtriturated with MeOH

Sources & evidence

ORD record
ord-a7d1ecb2054248789729ddbb5468ccf3
Source dataset
uspto-grants-2004_02
Patent number
US06693114B2

Reaction notes

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