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 2066575Notes

Reaction equation

HRID 2066575 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. ES MS M+1=466

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-bdc955b3b65b4dda934e93293844044a
Source dataset
uspto-grants-2012_10
Patent number
US08293731B2

Reaction notes

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