Sodium Hydroxide → HCID 178490750, compound

Participants

Reaction Conditions

Reaction Steps

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).

Provenance & Evidence