1,3,5-Triazine → (+/-)-1,2,5,10-Tetrahydro-9-isopropoxy-1-oxo-10-(2-trifluoromethylphenyl)-pyrido[4,3-b][1,6]naphthyridine

HRID 2413948Notes

Reaction equation

HRID 2413948 reaction equation
[CH:1]([O:4][C:5]1[N:14]=[CH:13][CH:12]=[C:11]2[C:6]=1[CH:7]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[C:27]([F:30])([F:29])[F:28])[C:8]([C:16]([O:18]CC)=O)=[C:9]([CH3:15])[NH:10]2)([CH3:3])[CH3:2].[H-].[Na+].[N:33]1C=NC=N[CH:34]=1>CN(C)C=O>[CH:1]([O:4][C:5]1[C:6]2[CH:7]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[C:27]([F:29])([F:28])[F:30])[C:8]3[C:16](=[O:18])[NH:33][CH:34]=[CH:15][C:9]=3[NH:10][C:11]=2[CH:12]=[CH:13][N:14]=1)([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 92621,3,5-TriazineHCID 24758Sodium hydrideHCID 128276CI 951

Product 1

HCID 9801169(+/-)-1,2,5,10-Tetrahydro-9-isopropoxy-1-oxo-10-(2-trifluoromethylphenyl)-pyrido[4,3-b][1,6]naphthyridine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

A solution of 11.3 g (27 mMole) ethyl (±)-1,4-dihydro-5-isopropoxy-2-methyl-4-(2-trifluoro methylphenyl)-1,6-naphthyridine-3-carboxylate in 200 ml dimethylformamide is added dropwise, under an atmosphere of nitrogen, to a suspension of 1.0 g (33 mMole) sodium hydride (80% in oil) in 20 ml dry dimethylformamide. After cessation of the gas evolution, the reaction mixture is stirred for 10 minutes at ambient temperature and subsequently 2.5 g (31 mMole) s-triazine in 20 ml dimethylformamide are added dropwise thereto. The reaction mixture is stirred for 16 hours at 105° C. and, after cooling, evaporated in a vacuum. The residue is chromatographed on silica gel with dichloromethane/methanol (95:5 v/v) and the fraction with an Rf of 0.6 is isolated and recrystallized from ethyl acetate/ethanol (9:1 v/v). There is obtained (±)-1,2,5,10-tetrahydro-9-isopropoxy-1-oxo-10-(2-trifluoromethylphenyl)-pyrido[4,3-b][1,6]naphthyridine in the form of colorless crystals; mp 315° C.

Workup

  1. stirringThe reaction mixture is stirred for 16 hours at 105° C.
  2. temperatureafter cooling
  3. customevaporated in a vacuum
  4. customThe residue is chromatographed on silica gel with dichloromethane/methanol (95:5 v/v)
  5. customthe fraction with an Rf of 0.6 is isolated
  6. customrecrystallized from ethyl acetate/ethanol (9:1 v/v)

Sources & evidence

ORD record
ord-70fe502511ae468d96ce651620a81110
Source dataset
uspto-grants-1988_01
Patent number
US04720499

Reaction notes

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