Methylamine → Methyl 6-(3-chloro-4-fluorobenzyl)-4-hydroxy-2-[4-(methylamino)butyl]-3,5-dioxo-2,3,5,6,7,8-hexahydro-2,6-naphthyridine-1-carboxylate

HRID 17993Notes

Reaction equation

HRID 17993 reaction equation
Cl[CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[C:15](=[O:16])[C:14]([OH:17])=[C:13]2[C:8]([CH2:9][CH2:10][N:11]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([F:26])=[C:22]([Cl:27])[CH:21]=3)[C:12]2=[O:18])=[C:7]1[C:28]([O:30][CH3:31])=[O:29].[CH3:32][NH2:33]>O1CCCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[Cl:27][C:22]1[CH:21]=[C:20]([CH:25]=[CH:24][C:23]=1[F:26])[CH2:19][N:11]1[CH2:10][CH2:9][C:8]2[C:13](=[C:14]([OH:17])[C:15](=[O:16])[N:6]([CH2:5][CH2:4][CH2:3][CH2:2][NH:33][CH3:32])[C:7]=2[C:28]([O:30][CH3:31])=[O:29])[C:12]1=[O:18]

Participants

5

Reactant 2

HCID 6329MethylamineHCID 66997340Methyl 2-(4-chlorobutyl)-6-(3-chloro-4-fluorobenzyl)-4-hydroxy-3,5-dioxo-2,3,5,6,7,8-hexahydro-2,6-naphthyridine-1-carboxylate

Product 1

HCID 66997664Methyl 6-(3-chloro-4-fluorobenzyl)-4-hydroxy-2-[4-(methylamino)butyl]-3,5-dioxo-2,3,5,6,7,8-hexahydro-2,6-naphthyridine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

A mixture of methyl 2-(4-chlorobutyl)-6-(3-chloro-4-fluorobenzyl)-4-hydroxy-3,5-dioxo-2,3,5,6,7,8-hexahydro-2,6-naphthyridine-1-carboxylate (0.10 g, 0.21 mmol), methylamine in tetrahydrofuran (1 mL, 2M), and tetra-n-butylammonium iodide in tetrahydrofuran (5 mL) was heated at 60° C. for 3 days. The reaction mixture was concentrated under vacuum. The residue was partitioned between dichloromethane and saturated aqueous sodium bicarbonate. The organic extract was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum to provide the title compound. This was used in the following step without further purification.

Workup

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. customThe residue was partitioned between dichloromethane and saturated aqueous sodium bicarbonate
  3. extractionThe organic extract
  4. washwas washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-c9cadc2ec735441d84b86d9654f6ffe4
Source dataset
uspto-grants-2010_06
Patent number
US07741315B2

Reaction notes

Loading…