Raltegravir

Base Information

• Chemical Name: Raltegravir
• CAS No.: 518048-05-0
• Molecular Formula: C20H21FN6O5
• Molecular Weight: 444.422
• Mol file: 518048-05-0.mol

Synonyms:5-Hydroxy-2-[1-[[(5-Methyl-1,3,4-oxadiazol-2-yl)carbonyl]amino]-1-methylethyl]-N-(4-fluorobenzyl)-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide;N-(4-Fluorobenzyl)-5-hydroxy-1-methyl-2-[1-methyl-1-[[(5-methyl-1,3,4-oxadiazol-2-yl)carbonyl]amino]ethyl]-6-oxo-1,6-dihydropyrimidine-4-carboxamide;4-Pyrimidinecarboxamide,N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-2-[1-methyl-1-[[(5-methyl-1,3,4-oxadiazol-2-yl)carbonyl]amino]ethyl]-6-oxo-;

Chemical Property of Raltegravir

Chemical Property:

• Melting Point: 216 °C(Solv: isopropanol (67-63-0))
• Refractive Index: 1.65
• PKA: 4.50±1.00(Predicted)
• PSA: 152.24000
• Density: 1.46 g/cm³
• LogP: 1.69330
• Storage Temp.: -20°C Freezer
• Solubility.: DMSO (Slightly), Methanol (Very Slightly)

Purity/Quality:

99% ^*data from raw suppliers

Raltegravir ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: Joining maraviroc as a unique approach to battling HIV-1, raltegravir, an inhibitor of HIV-1 integrase, represents the first in its class to be developed and launched as a combination treatment with other antiretroviral agents (NRTIs, NNRTIs, and PIs). HIV-1 integrase is essential for replication of the virus as a virally encoded enzyme that integrates the viral DNA into the genome of the host cell. Inhibition of HIV-1 integrase prevents the two-step process of endonucleolytic removal of the terminal dinucleotide from each 3′end of the viral DNA followed by the covalent integration of the viral DNA, at these modified 3′ends, into the host DNA, thereby representing a viable intervention in the viral life cycle. In vitro, raltegravir inhibited the strand transfer activity of HIV-1 integrase with an IC50 of 2–7nM with ＞ 1,000-fold selectivity over other phosphoryltransferases. In addition, its in vitro IC95 for HIV-1 in 10% fetal bovine serum and 50% human serum was 19 and 33 nM, respectively. Raltegravir was well tolerated with no dose-related toxicities and a safety profile comparable to placebo. The most common clinical adverse events were diarrhea, nausea, vomiting, fatigue, headache, flushing, pruritus, and injection-site reactions.
• Uses: Raltegravir (MK-0518) is a potent integrase (IN) inhibitor for WT and S217Q PFV IN. Raltegravir (MK-0518, Isentress) is a potent integrase (IN) inhibitor for WT and S217Q PFV IN with IC50 of 90 nM and 40 nM, respectively.
• Drug interactions: Potentially hazardous interactions with other drugs Antibacterials: concentration reduced by rifampicin, consider increasing raltegravir dose. Antivirals: avoid with fosamprenavir. Orlistat: absorption of raltegravir possibly reduced. Ulcer-healing drugs: concentration increased by omeprazole and famotidine.

Technology Process of Raltegravir

There total 59 articles about Raltegravir 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: 95.0%

5-methyl-1,3,4-oxadiazole-2-carboxylic acid chloride (889131-28-6) + 2-(1-amino-1-methyl-ethyl)-N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-4-pyrimidinecarboxamide (518048-03-8) → raltegravir (518048-05-0)

Guidance literature:

2-(1-amino-1-methyl-ethyl)-N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-4-pyrimidinecarboxamide; With 4-methyl-morpholine; In tetrahydrofuran; at 0 - 5 ℃; for 0.166667h;

5-methyl-1,3,4-oxadiazole-2-carboxylic acid chloride; In tetrahydrofuran; at 0 - 5 ℃; for 1.83333h;

With hydrogenchloride; potassium hydroxide; more than 3 stages;

Reference yield: 95.0%

5-methyl-1,3,4-oxadiazole-2-carboxylic acid chloride (889131-28-6) → raltegravir (518048-05-0)

Guidance literature:

2-(1-amino-1-methyl-ethyl)-N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-4-pyrimidinecarboxamide; With 4-methyl-morpholine; In tetrahydrofuran; at 0 - 5 ℃; for 0.166667h;

5-methyl-1,3,4-oxadiazole-2-carboxylic acid chloride; In tetrahydrofuran; at 0 - 5 ℃; for 1.83333h;

Reference yield: 94.0%

N-(4-fluorobenzyl)-2-(2-(5-methyl-1,3,4-oxadiazole-2-carboxamido)propan-2-yl)-1,6-dihydro-5-hydroxy-6-oxopyrimidine-4-carboxamide + trimethylsulfoxonium iodide (1774-47-6) → raltegravir (518048-05-0)

Guidance literature:

With magnesium hydroxide; In water; at 100 ℃; for 7h;

upstream raw materials:

5-methyl-1,3,4-oxadiazole-2-carboxylic acid chloride

2-(1-amino-1-methyl-ethyl)-N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-4-pyrimidinecarboxamide

C₂₅H₂₉FN₆O₆

methyl 5-(benzoyloxy)-1-methyl-2-(1-methyl-1-{[(5-methyl-1,3,4-oxadiazol-2-yl)carbonyl]amino}ethyl)-6-oxo-1,6-dihydropyrimidine-4-carboxylate

Downstream raw materials:

raltegravir diethylamine salt

raltegravir diisopropylamine salt

raltegravir tert-butylamine salt

N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-(1-methyl-1-{[(5-methyl-1,3,4-oxadiazol-2-yl)carbonyl] amino}ethyl)-6-oxo-1,6-dihydropyrimidine-4-carboxamide sodium salt

Refernces

• 1、 Karumanchi, Kishore,Nangi, Gangadhara Bhima Shankar,Danda, Subba Reddy,Chavakula, Ramadas,Korupolu, Raghu Babu,Bonige, Kishore Babu. "A Facile Synthesis of Raltegravir Potassium—An HIV Integrase Inhibitor". . p. 2683 - 2690. Retrieved 2019/08/21.
• 2、 Rao, S. Venkat,Potluri, Vamsi Krishna,Potluri, Ramesh Babu. "A newfangled synthesis of integrase inhibitor drug substance raltegravir potassium". . p. 2618 - 2622. Retrieved 2019/10/02.