Sodium Hydroxide → HCID 178490750, compound

HRID 1798910Notes

Reaction equation

HRID 1798910 reaction equation
[CH3:1][O:2][C:3]1[CH:29]=[CH:28][C:6]([CH2:7][N:8]2[CH2:17][C:16]3[CH2:15][CH:14]([C:18]([O:20]CC)=[O:19])[C:13]4=[N:23][NH:24][N:25]=[C:11]([C:12]=34)[C:10]([S:26][CH3:27])=[N:9]2)=[CH:5][CH:4]=1.[OH-].[Na+]>C(O)C.O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[CH2:17][C:16]3[CH2:15][CH:14]([C:18]([OH:20])=[O:19])[C:13]4=[N:23][NH:24][N:25]=[C:11]([C:12]=34)[C:10]([S:26][CH3:27])=[N:9]2)=[CH:28][CH:29]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 178468474HCID 178468474, compound

Product 1

HCID 178490750HCID 178490750, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

The crude ethyl 6-(4-methoxybenzyl)-4-(methylthio)-6,7,8,9-tetrahydro-2H-1,2,3,5,6-pentaazabenzo[cd]azulene-9-carboxylate (24 g), was dissolved in ethanol (250 mL) and sodium hydroxide (27.11 g, 677.75 mmol) in water (250 mL) was added to it. The reaction mixture was then stirred at 60° C. for 2 h. Ethanol was removed under reduced pressure and the aqueous layer was acidified using 10% citric acid solution. The aqueous layer was then extracted with dichloromethane (250 mL×3); the combined organic layer was washed with water (500 mL×2) followed by brine (500 mL), dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to give a residue as 6-(4-methoxybenzyl)-4-(methylthio)-6,7,8,9-tetrahydro-2H-1,2,3,5,6-pentaazabenzo[cd]azulene-9-carboxylic acid. To the residue (24 g) was added 4M HCl indioxane—(500 mL) and the mixture was refluxed for 16 h. Solvent was removed under reduced pressure and saturated NaHCO3 solution (250 mL) was added to the residue. The mixture was then extracted using dichloromethane (200 mL×3). The combined organic layer was washed with water (500 mL), brine (500 mL), dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography (using 0-10% tetrahydrofuran in dichloromethane) to give a solid and the solid was further titurated with n-pentane to provide pure 6-(4-methoxybenzyl)-4-(methylthio)-6,7,8,9-tetrahydro-2H-1,2,3,5,6-pentaazabenzo[cd]azulene (6.0 g, 29.2% yield over four steps). LCMS [M+H]: 342, HPLC: 97.65% (254 nm), 1H NMR (DMSO-d6, 400 MHz): δ 12.97 (bs, 1H), 7.24 (d, J=8.8 Hz, 2H), 6.89 (d, J=8.4 Hz, 2H), 4.91 (s, 2H), 3.72 (s, 3H), 3.55 (d, J=7.2 Hz, 2H), 2.90-2.80 (m, 2H), 2.45 (s, 3H), 2.0-1.9 (m, 2H).

Workup

  1. customEthanol was removed under reduced pressure
  2. extractionThe aqueous layer was then extracted with dichloromethane (250 mL×3)
  3. washthe combined organic layer was washed with water (500 mL×2)
  4. dry with materialdried over anhydrous sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-89baf04deb594817ba494b0ceaab15b1
Source dataset
uspto-grants-2013_01
Patent number
US08343983B2

Reaction notes

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