4-Chlorobenzylamine → N-(4-Chlorobenzyl)-6-(3-hydroxy-1-propynyl)-1-methyl-4-oxo-1,4-dihydro[1,5]-naphthyridine-3-carboxamide

HRID 1070658Notes

Reaction equation

HRID 1070658 reaction equation
C[Al](C)C.[Cl:5][C:6]1[CH:13]=[CH:12][C:9]([CH2:10][NH2:11])=[CH:8][CH:7]=1.[OH:14][CH2:15][C:16]#[C:17][C:18]1[N:19]=[C:20]2[C:25](=[CH:26][CH:27]=1)[N:24]([CH3:28])[CH:23]=[C:22]([C:29](OCC)=[O:30])[C:21]2=[O:34]>C(Cl)Cl>[Cl:5][C:6]1[CH:13]=[CH:12][C:9]([CH2:10][NH:11][C:29]([C:22]2[C:21](=[O:34])[C:20]3[C:25](=[CH:26][CH:27]=[C:18]([C:17]#[C:16][CH2:15][OH:14])[N:19]=3)[N:24]([CH3:28])[CH:23]=2)=[O:30])=[CH:8][CH:7]=1

Participants

5

Reactant 3

HCID 660364-ChlorobenzylamineHCID 16682925TrimethylaluminumHCID 22397164Ethyl 6-(3-Hydroxy-1-propynyl)-1-methyl-4-oxo-1,4-dihydro[1,5]naphthyridine-3-carboxylate

Product 1

HCID 10068427N-(4-Chlorobenzyl)-6-(3-hydroxy-1-propynyl)-1-methyl-4-oxo-1,4-dihydro[1,5]-naphthyridine-3-carboxamideYield 52%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trimethylaluminum (2M in toluene, 42 μL) is added dropwise to a room temperature solution of 4-chlorobenzylamine (17 μL) in CH2Cl2 (1 mL) under nitrogen. The solution is stirred for 5 minutes before the addition in one portion of ethyl 6-(3-hydroxy-1-propynyl)-1-methyl-4-oxo-1,4-dihydro[1,5]naphthyridine-3-carboxylate (Preparation 60, 20 mg). The resulting suspension is stirred at room temperature for 3.5 h. The reaction mixture is partitioned with dil. aq. HCl (2 mL) and extracted with CH2Cl2 (2×2 mL). After drying over MgSO4, the extracts are concentrated under vacuum. The crude residue is purified by flash chromatography (9 g silica, 10% methanol/CH2Cl2) to give 14 mg (52%) of the title compound as a It. yellow solid. Physical Characteristics: Rf (15% methanol/CH2Cl2)=0.53; 1H NMR (DMSO-d6) δ10.32, 8.90, 8.31, 7.90, 7.40, 7.36, 5.5, 4.58, 4.39, 4.01; HRMS (FAB) m/z 382.0963 (C20H16ClN3O3+H). Anal. Found (C20H16ClN3O3.0.24 H2O): C, 62.21; H, 4.21; N, 10.75.

Workup

  1. customThe reaction mixture is partitioned with dil. aq. HCl (2 mL)
  2. extractionextracted with CH2Cl2 (2×2 mL)
  3. dry with materialAfter drying over MgSO4
  4. concentrationthe extracts are concentrated under vacuum
  5. customThe crude residue is purified by flash chromatography (9 g silica, 10% methanol/CH2Cl2)

Sources & evidence

ORD record
ord-23d672ddbba14905bf1f24fd086ac24d
Source dataset
uspto-grants-2005_06
Patent number
US06903097B2

Reaction notes

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