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

HRID 2120770Notes

Reaction equation

HRID 2120770 reaction equation
[Cl:1][C:2]1[CH:28]=[CH:27][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:19](=[O:20])[C:18]3[C:13](=[N:14][C:15]([CH3:25])=[C:16]([C:21]#[C:22][CH2:23][OH:24])[CH:17]=3)[N:12]([CH3:26])[CH:11]=2)=[O:9])=[CH:4][CH:3]=1>C(Cl)Cl.CO.[Pd]>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:19](=[O:20])[C:18]3[C:13](=[N:14][C:15]([CH3:25])=[C:16]([CH2:21][CH2:22][CH2:23][OH:24])[CH:17]=3)[N:12]([CH3:26])[CH:11]=2)=[O:9])=[CH:27][CH:28]=1

Participants

5

Reactant 1

HCID 5276328N-[(4-chlorophenyl)methyl]-6-(3-hydroxyprop-1-ynyl)-1,7-dimethyl-4-oxo-1,8-naphthyridine-3-carboxamide

Product 1

HCID 5276329N-[(4-chlorophenyl)methyl]-6-(3-hydroxypropyl)-1,7-dimethyl-4-oxo-1,8-naphthyridine-3-carboxamideYield 66.7%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of N-(4-chlorobenzyl)-6-(3-hydroxy-1-propynyl)-1,7-dimethyl4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxamide (0.12 g, 0.30 mmol) in CH2Cl2 (20 mL) and MeOH (3 mL) is added 10% Pd/C (21 mg). The reaction is subjected to hydrogenation at 18 psi for 30 min. The reaction is filtered over Celite and monitored to determine the extent of the reaction. Fresh catalyst is added and the reaction is placed under hydrogen at 18 psi again. After another 30 minutes, the reaction is complete. The reaction is filtered over Celite. The filter cake is rinsed thoroughly with CH2Cl2, and MeOH. The filtrate is concentrated in vacuo and the residue is then dissolved in CH2Cl2 and adsorbed onto silica. Purification by chromatography (eluent 1% MeOH/CH2Cl2 (1 L), 2% MeOH/CH2Cl2 (1 L), 4% MeOH/CH2Cl2 (1 L)) affords the desired product as a white solid (0.079 g, 0.20 mmol, 66%). Physical characteristics are as follows: m.p. 176-177° C.; 1H NMR (300 MHz, DMSO-d6) δ10.30, 8.98, 8.35, 7.41, 7.36, 4.59, 4.56, 4.01, 3.47, 2.82, 2.67, 1.75; IR (drift) 1658, 1609, 1556, 1531, 1503, 1458, 1420, 1357, 1333, 1260, 1095, 1056, 1017, 811, 701 cm−1; MS (ESI) m/z 400.1 (M+H)+, 398.1 (M-H); HRMS (FAB) calcd for C21H22ClN3O3+H1 400.1428, found 400.1434.

Workup

  1. filtrationThe reaction is filtered over Celite and
  2. customthe extent of the reaction
  3. additionFresh catalyst is added
  4. waitAfter another 30 minutes
  5. filtrationThe reaction is filtered over Celite
  6. washThe filter cake is rinsed thoroughly with CH2Cl2, and MeOH
  7. concentrationThe filtrate is concentrated in vacuo
  8. dissolutionthe residue is then dissolved in CH2Cl2
  9. customPurification by chromatography (eluent 1% MeOH/CH2Cl2 (1 L), 2% MeOH/CH2Cl2 (1 L), 4% MeOH/CH2Cl2 (1 L))

Sources & evidence

ORD record
ord-c791036a25bd4cfb9664d97f61034555
Source dataset
uspto-grants-2004_02
Patent number
US06693114B2

Reaction notes

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