Midazolam maleate salt
- CAS No.
- 59467-94-6
- Chemical Name:
- Midazolam maleate salt
- Synonyms
- midazolammaleate;dormicum;Ro-21-3981;ro21-3981/001;dormicummaleate;MIDAZOLAM MALEATE SALT;[13C6]-Midazolam maleate salt;Midazolam maleate salt USP/EP/BP;midazolam maleate--dea schedule iv item;DL-A-LYSOPHOSPHATIDYLCHOLINE-*GAMMA-O-HE XADECYL
- CBNumber:
- CB5285259
- Molecular Formula:
- C22H17ClFN3O4
- Molecular Weight:
- 441.84
- MDL Number:
- MFCD00941440
- MOL File:
- 59467-94-6.mol
- MSDS File:
- SDS
| Melting point | 114-117° (solvated) |
|---|---|
| storage temp. | 2-8°C |
| solubility | DMSO (Slightly), Methanol (Slightly) |
| form | Solid |
| color | White to Off-White |
| Stability | Hygroscopic |
| CAS DataBase Reference | 59467-94-6(CAS DataBase Reference) |
| FDA UNII | 77520S18SE |
SAFETY
Risk and Safety Statements
| Symbol(GHS) |  GHS07 |
|---|---|
| Signal word | Warning |
| Hazard statements | H302 |
| Precautionary statements | P201-P260-P263-P264-P270-P308+P313-P201-P202-P281-P308+P313-P405-P501-P264-P270-P301+P312-P330-P501-P261-P271-P304+P340-P312-P403+P233-P405-P501 |
| Hazard Codes | Xn |
| Risk Statements | 22 |
| Safety Statements | 36 |
| RIDADR | 3249 |
| WGK Germany | 3 |
| RTECS | NI2922200 |
| HazardClass | 6.1(b) |
| PackingGroup | III |
| Toxicity | LD50 in male mice (mg/kg): 760 orally; 86 i.v. (Pieri) |
Midazolam maleate salt Chemical Properties,Uses,Production
Description
Midazolam maleate, 8- chloro-6-(2-fluorophenyl)?1-methyl-4Himidazo-benzodiazepine maleate , is a stable, water-soluble powder. The solubility in water depends on pH:≈85 mg/mL at pH 2.7 and 0.3 mg/mL at pH 7.6. The maleate is subject to reversible ring opening. Below pH4 the ring is open; above pH 4 the cyclic form is present. The anesthetic formulation is a buffered aqueous solution containing 2.5 mg/mL at pH 3.5.
Originator
Dormicum,Roche,Switz.,1982
Uses
Sedative; ligand GABA receptor benzodiazepine modulatory site
Manufacturing Process
Acetic anhydride (7 ml) was added to a solution of 6.16 g of crude 2-
aminomethyl-7-chloro-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-benzodiazepine
in 200 ml of methylene chloride. The solution was added to 200 ml of
saturated aqueous sodium bicarbonate and the mixture was stirred for 20
minutes. The organic layer was separated, washed with sodium bicarbonate,
dried over sodium sulfate and evaporated to leave resinous 2-
acetylaminomethyl-7-chloro-2,3-dihydro-5-(2-fluorophenyl)-lH -l,4-
benzodiazepine. This material was heated with 40 g of polyphosphoric acid at
150°C for 10 minutes. The cooled reaction mixture was dissolved in water,
made alkaline with ammonia and ice and extracted with methylene chloride.
The extracts were dried and evaporated and the residue was
chromatographed over 120 g of silica gel using 20% methanol in methylene
chloride. The clean fractions were combined and evaporated to yield resinous
8-chloro-3a,4-dihydro-6-(2-fluorophenyl)-1- methyl-4H-imidazo[1,5-a][1,4] -
benzodiazepine.
A mixture of this material with 500 ml of toluene and 30 g of manganese
dioxide was heated to reflux for 1? hours. The manganese dioxide was
separated by filtration over Celite. The filtrate was evaporated and the residue
was crystallized from ether to yield 8-chloro-6-(2-fluorophenyl)-1-methyl-4Himidazo[1,5-a][1,4]benzodiazepine, melting point 152°C to 154°C. The
analytical sample was recrystallized from methylene chloride/hexane.
A warm solution of 6.5 g (0.02 mol) of 8-chloro-6-(2-fluorophenyl)-1-methyl-
4H-imidazo[1,5-a] [1,4]-benzodiazepine in 30 ml of ethanol was combined
with a warm solution of 2.6 g (0.022 mol) of maleic acid in 20 ml of ethanol.
The mixture was diluted with 150 ml of ether and heated on the steam bath
for 3 minutes. After cooling, the crystals were collected, washed with ether
and dried in vacuo to yield 8-chloro-6-(2-fluorophenyl)-1-methyl-4Himidazo[1.5-a] [1,4]-benzodiazepine maleate, melting point 148°C to 151°C.
Therapeutic Function
Anesthetic
Biochem/physiol Actions
Sedative/Hypnotic; ligand for the GABAA receptor benzodiazepine modulatory site; CYP3A4 substrate.
Synthesis
The preparation starts with 7-chloro-
5-(2-fluorophenyl)?1,3-dihydro-2H-1,4-
benzodiaze-pinone . For the literature, also
see .
Midazolam is approximately twice as active
as diazepam, causes less pain at the injection
site, and has a shorter half-life than diazepam.
Side effects: dose-dependent cerebral depression
with tranquilization, sedation, and dryness.
Reduction in blood pressure, respiratory depression,
and cardiovascular effects were slight.
Midazolam maleate salt Preparation Products And Raw materials
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