132236-18-1

Basic information

• Product Name: Zifrosilone
• Synonyms: Zifrosilone;MDL73745
• CAS NO: 132236-18-1
• Molecular Formula: C₁₁H₁₃F₃OSi
• Molecular Weight: 246.303
• Mol File: 132236-18-1.mol
• Article Data: 5

Chemical Properties

• Boiling Point: 215.3°Cat760mmHg
• Flash Point: 84°C
• Appearance: /
• Density: 1.11g/cm³
• Vapor Pressure: 0.149mmHg at 25°C
• Refractive Index: 1.448
• CAS DataBase Reference: Zifrosilone(CAS DataBase Reference)
• NIST Chemistry Reference: Zifrosilone(132236-18-1)
• EPA Substance Registry System: Zifrosilone(132236-18-1)

Safety Data

• Hazardous Substances Data: 132236-18-1(Hazardous Substances Data)

Usage

Originator

Zifrosilone,Marion Merrell Dow

Uses

Inhibitor (acetylcholinesterase).

Manufacturing Process

3-Trimethylsilyl-bromobenzene:A mixture of 1,3-dibromobenzene (25.0 g, 106.4 mmol) and trimethylsilylchloride (11.6 g, 106.4 mmol) in diethyl ether (50 ml) was added dropwise in 1.5 hours on magnesium (2.59 g, 106.4 mmol) in diethyl ether (25 ml). Then the mixture was refluxed for 18 hours, cooled to 0°C, treated with 4 N HCl (75 ml). The organic layer was separated, washed with water, brine, dried over MgSO 4 and concentrated. 3-Trimethylsilylbromobenzene was obtained by fractional distillation as a colorless oil (13.4 g, 55% yield, b.p.: 55-62°C/0.8 mmHg.2,2,2-Trifluoro-1-(3-trimethylsilylphenyl)ethanone:To a solution of 3-trimethylsilylbromobenzene (7.62 g, 33.3 mmol) in diethyl ether (35 ml) was added 1.5 M n-butyl lithium in hexane (22.2 ml, 33.3 mmol) at 0°C over 10 min. Then the mixture was allowed to react 15 min at room temperature, cooled to -78°C and ethyl trifluoroacetate (14.2 g, 100 mmol) was added over 5 min. Then the mixture was allowed to react 15 min at -78°C, the cooling bath was removed and when the temperature rose to 0°C. 3 N HCl (35 ml) was added dropwise. The organic layer was separated, washed with water, brine, dried over MgSO 4 and concentrated. Chromatography (silica gel, cyclohexane/diethyl ether: 90/10) followed by distillation under reduced pressure afforded the expected compound (zifrosilone) as a colorless oil (4.32 g, 53% yield), boiling point 120°C/0.8 mm Hg; Rf: 0.28 (cyclohexane/diethyl ether: 95/5).

Therapeutic Function

Acetylcholinesterase inhibitor

InChI:InChI=1/C11H13F3OSi/c1-16(2,3)9-6-4-5-8(7-9)10(15)11(12,13)14/h4-7H,1-3H3

Upstream product

• 81290-20-2 (trifluoromethyl)trimethylsilane 
• 655-26-5 m-bromotrifluoroacetone 
• 17878-47-6 (3-bromophenyl)trimethylsilane 
• 431-47-0 trifluoroacetic acid-methyl ester 
• 2060-89-1 m-bis(trimethylsilyl)benzene 
• 407-25-0 trifluoroacetic anhydride 
• 768-32-1 trimethylphenylsilane 
• 383-63-1 ethyl trifluoroacetate, 

Relevant articles and documents

Design, Synthesis, and Implementation of Sodium Silylsilanolates as Silyl Transfer Reagents

There is an increasing demand for facile delivery of silyl groups onto organic bioactive molecules. One of the common methods of silylation via a transition-metal-catalyzed coupling reaction employs hydrosilane, disilane, and silylborane as major silicon sources. However, the labile nature of the reagents or harsh reaction conditions sometimes render them inadequate for the purpose. Thus, a more versatile alternative source of silyl groups has been desired. We hereby report a design, synthesis, and implementation of storable sodium silylsilanolates that can be used for the silylation of aryl halides and pseudohalides in the presence of a palladium catalyst. The developed method allows a late-stage functionalization of polyfunctionalized compounds with a variety of silyl groups. Mechanistic studies indicate that (1) a nucleophilic silanolate attacks a palladium center to afford a silylsilanolate-coordinated arylpalladium intermediate and (2) a polymeric cluster of silanolate species assists in the intramolecular migration of silyl groups, which would promote an efficient transmetalation.

Difluoromethyl ketones: Potent inhibitors of wild type and carbamate-insensitive G119S mutant Anopheles gambiae acetylcholinesterase

Malaria is a devastating disease in sub-Saharan Africa, and current vector control measures are threatened by emerging resistance mechanisms. With the goal of developing new, selective, resistance-breaking insecticides we explored α-fluorinated methyl ketones as reversible covalent inhibitors of Anopheles gambiae acetylcholinesterase (AgAChE). Trifluoromethyl ketones 5 demonstrated remarkable volatility in microtiter plate assays, but 5c,e-h exhibited potent (1-100 nM) inhibition of wild type (WT) AgAChE and weak inhibition of resistant mutant G119S mutant AgAChE. Fluoromethyl ketones 10c-i exhibited submicromolar to micromolar inhibition of WT AgAChE, but again only weakly inhibited G119S AgAChE. Interestingly, difluoromethyl ketone inhibitors 9c and 9g had single digit nanomolar inhibition of WT AgAChE, and 9g had excellent potency against G119S AgAChE. Approach to steady-state inhibition was quite slow, but after 23 h incubation an IC50 value of 25.1 ± 1.2 nM was measured. We attribute the slow, tight-binding G119S AgAChE inhibition of 9g to a balance of steric size and electrophilicity. However, toxicities of 5g, 9g, and 10g to adult A. gambiae in tarsal contact, fumigation, and injection assays were lower than expected based on WT AgAChE inhibition potency and volatility. Potential toxicity-limiting factors are discussed.

ACETYLCHOLINESTERASE INHIBITORS

This invention relates to silylated aromatic fluoroketones possessing acetylcholinesterase-inhibiting properties and to their use in the treatment of Alzheimer disease and senile dementia