Sulfuric acid Mono-[7-oxo-2-(piperidin-4-ylcarbaMoyl)-1,6-diaza-bicyclo[3.2.1]oct-6-yl] ester

Base Information

• Chemical Name: Sulfuric acid Mono-[7-oxo-2-(piperidin-4-ylcarbaMoyl)-1,6-diaza-bicyclo[3.2.1]oct-6-yl] ester
• CAS No.: 1174018-99-5
• Molecular Formula: C12H20N4O6S
• Molecular Weight: 348.38
• Mol file: 1174018-99-5.mol

Synonyms:Sulfuric acid Mono-[7-oxo-2-(piperidin-4-ylcarbaMoyl)-1,6-diaza-bicyclo[3.2.1]oct-6-yl] ester;Sulfuric acid mono[(1R,2S,5R)-7-oxo-2-[(4-piperidinylamino)carbonyl]-1,6-diazabicyclo[3.2.1]oct-6-yl] ester;MK-7655(Relebactam)

Chemical Property of Sulfuric acid Mono-[7-oxo-2-(piperidin-4-ylcarbaMoyl)-1,6-diaza-bicyclo[3.2.1]oct-6-yl] ester

Chemical Property:

• PKA: -4.59±0.18(Predicted)
• PSA: 136.66000
• Density: 1.59
• LogP: 0.53390
• Storage Temp.: Hygroscopic, -20°C Freezer, Under inert atmosphere
• Solubility.: DMSO (Slightly), Water (Slightly)

Purity/Quality:

98%,99%, ^*data from raw suppliers

Relebactam ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: Relebactam (formerly known as MK-7655) is a novel,intravenous,class A and class C B-lactamase inhibitor and is currently under evaluation in combination with imipenem/cilastatin for the treatment of resistant Gram-negative infections.In vitro studies demonstrated that relebactam restored imipenem's activity against KPC-producing Enterobacteriacae，lowering imipenem MICs from 16-64 to 0.12-1mg/L at a concentration of 4 mg/L. Moreover, relebactam is able to lower imipenem MICs for P. aeruginosa，particularly in strains with depressed OprD expression and increased AmpC expression.Conversely, the addition of relebactam to imipenem does not seem to provide any adjunctive benefit against A.baumanii or S.maltophilia or against MBL-producing Enterobacteriacae.A non-inferiority, Phase 3 trial evaluating the efficacy and safety of imipenem/relebactam compared to piperacillin/tazobactam for the treatment of HAP and VAP(ClinicalTrials.gov Identifier: NCT02493764) is currently recruiting. A Phase 3 study evaluating the efficacy and safety of imipenem/relebactam (200/100-500/250 mg depending on renal function) compared to colistimethate sodium plus imipenem/cilastatin for the treatment of imipenem-resistant bacterial infections,including HAP, VAP, cIAIs and cUTIs, has recently been completed and results are pending(ClinicalTrials.gov Identifier: NCTO2452047).In Phase 2 trials, imipenem/relebactam was well tolerated, with diarrhea, nausea, vomiting and headache being the most commonly reported adverse events.
• Uses: Relebactam is a novel β-lactamase inhibitor in combination with Primaxin.
• Clinical Use: Recently, another carbapenem-β-lactamase inhibitor, imipenem/cilastatin-relebactam (RecarbrioTM), was approved by the FDA. Relebactam, a bicyclic diazabicyclooctane, is structurally related to avibactam but differs by the addition of a piperidine ring to the 2-position carbonyl group. Like meropenem- vaborbactam (VabomereTM), imipenem-relebactam(RecarbrioTM) is active against class A and class C carbapenemases and is approved for the treatment of multidrug-resistant intraabdominal infections secondary to Bacteroides caccae, Bacteroides fragilis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Bifidobacterium stercoris, Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Fusobacterium nucleatum, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Parabacteroides distasonis, and Pseudomonas aeruginosa and multidrug-resistant complicated urinary tract infections secondary to E. cloacae, E. coli, K. aerogenes, K. pneumoniae and P. aeruginosa.

Technology Process of Sulfuric acid Mono-[7-oxo-2-(piperidin-4-ylcarbaMoyl)-1,6-diaza-bicyclo[3.2.1]oct-6-yl] ester

There total 27 articles about Sulfuric acid Mono-[7-oxo-2-(piperidin-4-ylcarbaMoyl)-1,6-diaza-bicyclo[3.2.1]oct-6-yl] ester 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: 93.0%

tetrabutyl ammonium salt (25,5R)-4-tert-butyl{(6-sulfooxy-7-oxo-1,6-diazabicyclo[3.2.1]oct-2-ylcarbonyl)amino}piperidine-1-carboxylate (1174020-24-6) → (2S,5R)-sulfuric acid mono{[(4-aminopiperidin-4-yl)carbonyl]-7-oxo-1,6-diazabicyclo[3.2.1]oct-6-yl}ester (1174018-99-5)

Guidance literature:

With TMSI; In acetonitrile; at 0 - 5 ℃;

DOI:10.1021/ol4031606

Reference yield:

(2S,5R)-5-hydroxypiperidine-2-carboxylic acid (63088-78-8,448964-01-0,478409-64-2) → (2S,5R)-sulfuric acid mono{[(4-aminopiperidin-4-yl)carbonyl]-7-oxo-1,6-diazabicyclo[3.2.1]oct-6-yl}ester (1174018-99-5)

Guidance literature:

Multi-step reaction with 10 steps

1.1: sodium hydroxide / water; acetone / 23 - 30 °C / pH 10.2 - 10.7 / Inert atmosphere

2.1: 2-Nitrobenzenesulfonyl chloride; triethylamine / acetone; ethyl acetate / 20 - 28 °C / Inert atmosphere

3.1: tetrahydrofuran / 0.18 h / 72 °C / Inert atmosphere

4.1: dmap / tetrahydrofuran / 20 - 30 °C / Inert atmosphere

5.1: potassium carbonate / N,N-dimethyl acetamide / 60 - 70 °C / Inert atmosphere

6.1: lithium hydroxide / methanol / 50 °C

7.1: N-ethyl-N,N-diisopropylamine / dichloromethane / -18 - 0 °C / Inert atmosphere

8.1: hydrogen / tetrahydrofuran / 20 h / 23 °C / 3087.28 Torr

9.1: sulfur trioxide pyridine complex; α-picoline / tetrahydrofuran / 15 h / Inert atmosphere

9.2: 0.67 h / -10 °C

10.1: TMSI / acetonitrile / 0 - 5 °C

With α-picoline; dmap; hydrogen; sulfur trioxide pyridine complex; potassium carbonate; 2-Nitrobenzenesulfonyl chloride; triethylamine; N-ethyl-N,N-diisopropylamine; sodium hydroxide; lithium hydroxide; In tetrahydrofuran; methanol; dichloromethane; N,N-dimethyl acetamide; water; ethyl acetate; acetone; acetonitrile;

DOI:10.1021/ol4031606

Reference yield:

tert-butyl 4-((1R,2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamido)piperidine-1-carboxylate (1174020-63-3) → (2S,5R)-sulfuric acid mono{[(4-aminopiperidin-4-yl)carbonyl]-7-oxo-1,6-diazabicyclo[3.2.1]oct-6-yl}ester (1174018-99-5)

Guidance literature:

Multi-step reaction with 3 steps

1: palladium on activated charcoal; hydrogen / methanol / 25 °C

2: sulfur trioxide pyridine complex; pyridine / 25 °C

3: trifluoroacetic acid / dichloromethane

With pyridine; palladium on activated charcoal; hydrogen; sulfur trioxide pyridine complex; trifluoroacetic acid; In methanol; dichloromethane;

DOI:10.1016/j.bmcl.2013.12.101

upstream raw materials:

tetrabutyl ammonium salt (25,5R)-4-tert-butyl{(6-sulfooxy-7-oxo-1,6-diazabicyclo[3.2.1]oct-2-ylcarbonyl)amino}piperidine-1-carboxylate

tert-butyl-4-({[(2S,5R)-7-oxo-6-(sulfooxy)-1,6-diazabicyclo[3.2.1]oct-2-yl]carbonyl}amino)piperidine-1-carboxylate

benzyl 4-aminopiperidine-1-carboxylate

tert-butyl (2S)-2-[({1-[(benzyloxy)carbonyl]piperidin-4-yl}amino)carbonyl]-5-oxopiperidine-1-carboxylate

Refernces

• 1、 -. "PROCESS FOR O-SULFONATION OF 1,6-DIAZABICYCLO[3.2.1]OCTANE COMPOUNDS". Page/Page column 7-8; 10-11. . Retrieved 2019/01/10.
• 2、 Miller, Steven P.,Zhong, Yong-Li,Liu, Zhijian,Simeone, Michael,Yasuda, Nobuyoshi,Limanto, John,Chen, Zheng,Lynch, Joseph,Capodanno, Vincent. "Practical and cost-effective manufacturing route for the synthesis of a β-lactamase inhibitor". supporting information. p. 174 - 177. Retrieved 2014/01/23.