Efavirenz

Base Information

• Chemical Name: Efavirenz
• CAS No.: 154598-52-4
• Molecular Formula: C14H9ClF3NO2
• Molecular Weight: 315.679
• Hs Code.: 2934990002
• European Community (EC) Number: 620-492-6
• NSC Number: 742403
• UNII: JE6H2O27P8
• DSSTox Substance ID: DTXSID9046029
• Nikkaji Number: J727.577C
• Wikipedia: Efavirenz
• Wikidata: Q422645
• NCI Thesaurus Code: C29027
• RXCUI: 195085
• Pharos Ligand ID: FRVL6LWPXSL8
• Metabolomics Workbench ID: 42951
• ChEMBL ID: CHEMBL223228
• Mol file: 154598-52-4.mol

Synonyms:(s)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one;DMP 266;DMP-266;efavirenz;efavirenz, (R)-isomer;efavirenz, (S)-isomer;L 743,726;L 743726;L-743,726;L-743726;Stocrin;Sustiva

Chemical Property of Efavirenz

Chemical Property:

• Appearance/Colour: white to slightly pink crystalline powder
• Vapor Pressure: 8.53E-05mmHg at 25°C
• Melting Point: 139-141 °C
• Refractive Index: 1.58
• Boiling Point: 340.6 °C at 760 mmHg
• PKA: 10.2(at 25℃)
• Flash Point: 159.8 °C
• PSA: 38.33000
• Density: 1.53 g/cm³
• LogP: 4.21110
• Storage Temp.: -20°C Freezer
• Solubility.: DMSO: soluble15mg/mL, clear
• Water Solubility.: 8mg/L(temperature not stated)
• XLogP3: 4
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 1
• Exact Mass: 315.0273907
• Heavy Atom Count: 21
• Complexity: 519

Purity/Quality:

98% ^*data from raw suppliers

Efavirenz ^*data from reagent suppliers

Safty Information:

• Pictogram(s): N
• Hazard Codes: N
• Statements: 50
• Safety Statements: 61

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antiviral Agents
• Canonical SMILES: C1CC1C#CC2(C3=C(C=CC(=C3)Cl)NC(=O)O2)C(F)(F)F
• Isomeric SMILES: C1CC1C#C[C@]2(C3=C(C=CC(=C3)Cl)NC(=O)O2)C(F)(F)F
• Recent ClinicalTrials: Pharmacokinetic and Safety of Antiretroviral and Related Drugs in Lactating Women and Breastmilk Fed Infants
• Recent EU Clinical Trials: EFFICACY AND SAFETY CLINICAL TRIAL WITH EFAVIRENZ IN PATIENTS DIAGNOSED WITH ADULT NIEMANN-PICK TYPE C WITH COGNITIVE IMPAIRMENT
• Description: Efavirenz D5 was launched as Sustiva in the US for the treatment of infection by HIV, the virus causing AIDS, in combination with other anti-retroviral agents. Efavirenz D5 is a non-nucleoside reverse transcriptase inhibitor (NNRTI) belonging to the 3,1-benzoxazin-2-one chemical class. It is the third non-nucleoside reverse transcriptase inhibitor to have been launched to date, after Nevirapine (1996) and Delavirdine (1997), increasing the arsenal of anti-HIV drugs for treating infected patients in dual or triple combination with nucleoside or other non-nucleoside RTIs, or protease inhibitors. Efavirenz D5 can be obtained by two related ways of six steps from 4-chloroaniline ; one of them is based on asymmetric synthesis by enantioselective addition of an acetylide to a trifluoroacetophenone. The anti-HIV activity of Efavirenz D5 was demonstrated against most wild-type and clinical strains of HIV-1, including those with the most frequently observed mutations. Efavirenz D5 has a better pharmacokinetic profile when compared with the preceding drugs of this class ; in particular, in a long-term experiment conducted in cynomolgus monkeys, Efavirenz D5 was shown to easily cross the blood brain barrier leading to an increase of the antiviral concentration in cerebrospinal fluid.
• Uses: antiviral;reverse transcriptase inhibitor For use in combination treatment of HIV infection (AIDS) Efavirenz D5 is a nonnucleoside HIV-1 reverse transcriptase inhibitor. Antiviral
• Indications: Efavirenz (Sustiva) is approved for the therapy of HIV infection of adults and children and is also used for postexposure prophylaxis. It is the only NNRTI approved for once-daily dosing. Rash, although rarely severe, is a common adverse effect of efavirenz. Elevated liver enzymes and serum cholesterol also may occur. Central nervous system (CNS) effects in approximately half of patients may include dizziness, headache, insomnia, drowsiness, euphoria, agitation, impaired cognition, nightmares, vivid dreams, and hallucinations. These effects often subside after several weeks to months of therapy.
• Therapeutic Function: Antiviral
• Clinical Use: Treatment of HIV-1 infection in adults and children (in combination with other antiretroviral drugs)
• Drug interactions: Potentially hazardous interactions with other drugsAntibacterials: concentration of rifabutin reduced.Anticoagulants: possibly affects concentration of coumarins.Antidepressants: concentration reduced by St John’s wort - avoid.Antifungals: itraconazole, posaconazole and voriconazole concentration reduced; voriconazole increases efavirenz concentration - reduce dose of efavirenz by 50% and increase dose of voriconazole to 400 mg twice daily; possibly reduces caspofungin concentration - may possibly need to increase caspofungin dose.Antimalarials: concentration of artemether with lumefantrine reduced.Antipsychotics: possibly increased risk of ventricular arrhythmias with pimozide - avoid; possibly reduces aripiprazole concentration - increase aripiprazole doseAntivirals: concentration of atazanavir and boceprevir reduced - avoid; saquinavir concentration significantly reduced; concentration of daclatasvir, darunavir, dolutegravir, indinavir, lopinavir, telaprevir and possibly etravirine and maraviroc reduced - adjust daclatasvir, darunavir, dolutegravir, lopinavir, maraviroc and telaprevir dose, avoid with etravirine; concentration reduced by nevirapine; monitor LFTs when used in combination with ritonavir.Anxiolytics and hypnotics: risk of prolonged sedation with midazolam - avoid.Atovaquone: concentration of atovaquone reduced - avoid.Ciclosporin: concentration of ciclosporin possibly reduced.Cytotoxics: concentration of bosutinib possibly reduced - avoidErgot alkaloids: risk of ergotism - avoid.Grapefruit juice: concentration possiblyincreased.Guanfacine: concentration of guanfacine possibly reduced, increase dose of guanfacineOestrogens and progestogens: possibly reduced contraceptive effect.Orlistat: absorption possibly reduced by orlistat.Tacrolimus: possibly affects tacrolimus concentration.Ulipristal: possibly reduced contraceptive effect.

Technology Process of Efavirenz

There total 63 articles about Efavirenz which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 99.0%

bis(trichloromethyl) carbonate (32315-10-9) + (2S)-2-(2-amino-5-chlorophenyl)-4-cyclopropyl-1,1,1-trifluorobut-3-yn-2-ol (209414-27-7,927812-33-7,154598-58-0) → efavirenz (154598-52-4,154635-17-3)

Guidance literature:

With sodium hydrogencarbonate; In 1,2-dimethoxyethane; water; at -10 - 25 ℃; Product distribution / selectivity; Inert atmosphere;

Reference yield: 98.4%

phosgene (75-44-5) + (S)-2-(2-amino-5-chlorophenyl)-4-cyclopropyl-1,1,1-trifluorobut-3-yn-2-ol mesylate → efavirenz (154598-52-4,154635-17-3)

Guidance literature:

With potassium hydrogencarbonate; In tert-butyl methyl ether; water; at 7 - 17 ℃; for 4h; Product distribution / selectivity;

Reference yield: 98.0%

bis(phenyl) carbonate (102-09-0) + (αR)-2-amino-5-chloro-α-(2-cyclopropylethynyl)-α-(trifluoromethyl)benzenemethanol (927812-33-7,154598-58-0) → efavirenz (154598-52-4,154635-17-3)

Guidance literature:

With 1,8-diazabicyclo[5.4.0]undec-7-ene; In tetrahydrofuran; at 60 ℃; for 2h;

upstream raw materials:

(S)-6-chloro-4-(cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-1-<(4'-methoxyphenyl)methyl>-3,1-benzoxazin-2-one

phosgene

(2S)-2-(2-amino-5-chlorophenyl)-4-cyclopropyl-1,1,1-trifluorobut-3-yn-2-ol

4-Nitrophenyl chloroformate

Downstream raw materials:

piperidine

8-Hydroxyefavirenz

Refernces

• 1、 Thompson, Andrew S.,Corley, Edward G.,Huntington, Martha F.,Grabowski, E. J. J.. "Use of an Ephedrine Alkoxide to Mediate Enantioselective Addition of an Acetylide to a Prochiral Ketone: Asymmetric Synthesis of the Reverse Transcriptase Inhibitor L-743,726.". . p. 8937 - 8940. Retrieved 1995.
• 2、 -. "Efavirenz synthesis method and method for preparing intermediate of efavirenz". Paragraph 0051-0053. . Retrieved 2020/09/02.
• 3、 Okusu, Satoshi,Hirano, Kazuki,Yasuda, Yoshimasa,Tanaka, Junki,Tokunaga, Etsuko,Fukaya, Haruhiko,Shibata, Norio. "Alkynyl Cinchona Catalysts affect Enantioselective Trifluoromethylation for Efavirenz under Metal-Free Conditions". . p. 5568 - 5571. Retrieved 2016/11/17.