Dimethylformamide → HCID 18670681, compound

HRID 1059306Notes

Reaction equation

HRID 1059306 reaction equation
[C:1]([C:3]1[C:8]2[S:9][C:10]3[CH:16]=[CH:15][C:14]([C:17]([O:19][CH3:20])=[O:18])=[CH:13][C:11]=3[NH:12][C:7]=2[N:6]=[CH:5][CH:4]=1)#[N:2].[H-].[Na+].[CH3:23][O:24][CH2:25]Cl.[CH3:27]N(C)C=O>O>[C:1]([C:3]1[C:8]2[S:9][C:10]3[CH:16]=[CH:15][C:14]([C:17]([O:19][CH3:20])=[O:18])=[CH:13][C:11]=3[N:12]([CH2:27][CH2:25][O:24][CH3:23])[C:7]=2[N:6]=[CH:5][CH:4]=1)#[N:2]

Participants

6

Reactant 4

HCID 6228Dimethylformamide2×HCID 7864Chloromethyl Methyl EtherHCID 24758Sodium hydrideHCID 18670103HCID 18670103, compound

Product 1

HCID 18670681HCID 18670681, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of methyl 3-amino-4-(1-oxo-4-cyano-3-pyridylthio)benzoate in pyridine (20 ml) was added 5 ml of acetic anhydride and the resulting mixture was stirred for 16 hours. Then the reaction mixture was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (eluted with dichloromethane/ethyl acetate) to thereby give 0.45 g of methyl 3-acetamido-4-(1-oxo-4-cyano-3-pyridylthio)benzoate as a colorless solid. 0.079 g of sodium hydride was added in a nitrogen atmosphere to a solution of 0.45 g of methyl 3-acetamido-4-(1-oxo-4-cyano-3-pyridylthio)benzoate in N,N-dimethylformamide (15 ml) and the resulting mixture was stirred for 10 minutes. After adding 0.503 g of sulfur, the resulting mixture was stirred at 130° C. for 15 minutes. The reaction mixture was diluted with water and the crystals thus precipitated were taken up by filtration and washed with water. Thus 0.267 g of methyl 4-cyano-10H-pyrido[3,2-b][1,4]-benzothiazine-8-carboxylate was obtained as yellow crystals. To a solution of 0. 267 g of methyl 4-cyano-10H-pyrido[3,2-b][1,4]-benzothiazine-8-carboxylate in N,N-dimethylformamide (20 ml) were successively added in a nitrogen atmosphere 0.045 g of sodium hydride and a solution of 0.12 ml of chloromethyl methyl ether in N,N-dimethylformamide (9 ml) and the resulting mixture was stirred for 1 hour. Then the reaction mixture was diluted with water and eluted with ethyl acetate. The organic layer was washed with water and a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluted with n-hexane/dichloromethane) to thereby give 0.152 g of the title compound as pale yellow crystals.

Workup

  1. washeluted with ethyl acetate
  2. washThe organic layer was washed with water
  3. dry with materiala saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (eluted with n-hexane/dichloromethane)

Sources & evidence

ORD record
ord-d954348173764cc6a8069c8d42c973fb
Source dataset
uspto-grants-2003_02
Patent number
US06518423B1

Reaction notes

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