4H-IMIDAZO[1,5-A][1,4]BENZODIAZEPINE-3-CARBOXYLIC ACID, 8-FLUORO-5,6-DIHYDRO-5-METHYL-6-OXO-

Flumazenil acid is a metabolite of Flumazenil[1]. Flumazenil is a GABAA receptor antagonist[2].

Flumazenil (0.5 g, 1.7 mmol) was suspended in THF (50 mL). Sodium hydroxide (10 mL of a 2M solution in water) was added and the suspended solid dissolved. The mixture was stirred at room temperature until judged complete by thin layer chromatography (TLC). The solvent was removed in vacuo and the residue dissolved in water, treated with 2M hydrochloric acid to precipitate the acid. The solid was filtered off and dried in vacuo to give a colourless solid (0.45 g, 100percent). The acid from 3.1, (300 mg, 1.4 mmol) was dissolved in dichloromethane (5 mL) and thionyl chloride (5 mL). Dry DMF (five drops) was added and the mixture was heated at reflux for 2 hours. The solvent was removed in vacuo and the gummy residue redissolved in dichloromethane and used immediately. The solution was treated with e.g. 2-fluoroethanol (1.1 g, 17 mmol, 1 mL). The mixture was stirred at room temperature for 16 hours. The solvent was removed in vacuo and the product isolated by column chromatography to give FFMZ in 96% yield.Flumazenil (0.5 g, 1.7 mmol) was suspended in THF (50 mL). Sodium hydroxide (10 mL of a 2M solution in water) was added and the suspended solid dissolved. The mixture was stirred at room temperature until judged complete by thin layer chromatography (TLC). The solvent was removed in vacuo and the residue dissolved in water, treated with 2M hydrochloric acid to precipitate the acid. The solid was filtered off and dried in vacuo to give a colourless solid (0.45 g, 100%). 1H NMR (CD3OD): dH 3.24 (3H. s, CH3), 4.62 (1H, br d, J = 15.4 Hz, CHaHb), 5.19 (1H, br d, J = 15.4 Hz, CHaHb), 7.62 (1H, ddd, JHF = 12.5 Hz, JHH = 7.7 and 3.1 Hz, CFCHCH), 7.79 (1H, dd, JHF = 8.9 Hz, JHH = 3.1 Hz, CCHCF), 7.87 (1H, dd, JHF = 9.1 Hz, JHH = 4.5 Hz, CHCHCF), and 9.63 (1H, s, NCHN).

Molecular Weight:275.23
XLogP3:0.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:1
Exact Mass:275.07061935
Monoisotopic Mass:275.07061935
Topological Polar Surface Area:75.4
Heavy Atom Count:20
Complexity:433
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes