Triethylamine → N-[(4-chlorophenyl)methyl]-6-iodo-7-methoxy-1-methyl-4-oxo-1,8-naphthyridine-3-carboxamide

HRID 1280463Notes

Reaction equation

HRID 1280463 reaction equation
[I:1][C:2]1[CH:3]=[C:4]2[C:9](=[N:10][C:11]=1[O:12][CH3:13])[N:8]([CH3:14])[CH:7]=[C:6]([C:15]([OH:17])=O)[C:5]2=[O:18].C1C=CC(OP(Cl)(OC2C=CC=CC=2)=O)=CC=1.C(N(CC)CC)C.[Cl:43][C:44]1[CH:51]=[CH:50][C:47]([CH2:48][NH2:49])=[CH:46][CH:45]=1>C(Cl)Cl>[Cl:43][C:44]1[CH:51]=[CH:50][C:47]([CH2:48][NH:49][C:15]([C:6]2[C:5](=[O:18])[C:4]3[C:9](=[N:10][C:11]([O:12][CH3:13])=[C:2]([I:1])[CH:3]=3)[N:8]([CH3:14])[CH:7]=2)=[O:17])=[CH:46][CH:45]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 660364-ChlorobenzylamineHCID 75654Diphenyl chlorophosphateHCID 120933156-Iodo-7-methoxy-1-methyl-4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxylic acid

Product 1

HCID 5276330N-[(4-chlorophenyl)methyl]-6-iodo-7-methoxy-1-methyl-4-oxo-1,8-naphthyridine-3-carboxamideYield 29%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

6-Iodo-7-methoxy-1-methyl-4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxylic acid (1.50 g) is dissolved in CH2Cl2 (0.5 L). To this is added diphenyl chloridophosphate (1.5 mL) and triethyl amine (1.7 mL). The resulting mixture is stirred at room temperature for 2 h, followed by the addition of 4-chlorobenzyl amine (1.2 mL). The reaction is stirred for additional 3 h, then washed with 1N HCl, 1N NaOH, brine, dried (MgSO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography (heptane/EtOAc 4/1, 1/1, CH2Cl2/MeOH 19/1) and the product is then triturated with MeOH to afford 592 mg (29%) of N-(4-chlorobenzyl)-6-iodo-7-methoxy-1-methyl-4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxamide. Physical characteristics are as follows: 1H NMR (CDCl3) δ 10.20, 9.01, 8.81, 7.32-7.27, 4.62, 4.13, 3.96; 13C NMR (CDCl3) δ 175.24, 164.41, 162.95, 159.66, 148.69, 147.78, 147.69, 137.26, 132.85, 128.93, 128.69, 118.76, 113.68, 55.77, 42.58, 39.12; IR (diffuse reflectance) 2296, 1908, 1665, 1613, 1593, 1570, 1544, 1507, 1491, 1460, 1447, 1386, 1286, 1278, 809, cm−1; MS (FAB) m/z 484 (MH+), 486, 485, 484, 344, 343, 217, 133, 127, 125, 55; Anal. calcd for C18H15ClIN3O3: C, 44.70; H, 3.13; N, 8.69. Found: C, 44.38; H, 3.17; N, 8.62.

Workup

  1. stirringThe reaction is stirred for additional 3 h
  2. washwashed with 1N HCl, 1N NaOH, brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified by silica gel chromatography (heptane/EtOAc 4/1, 1/1, CH2Cl2/MeOH 19/1)
  7. customthe product is then triturated with MeOH

Sources & evidence

ORD record
ord-25353e18ae2948cb94ef3f181d3b7dfd
Source dataset
uspto-grants-2002_09
Patent number
US06451811B2

Reaction notes

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