Ciluprevir

Base Information

• Chemical Name: Ciluprevir
• CAS No.: 300832-84-2
• Molecular Formula: C₄₀H₅₀N₆O₈S
• Molecular Weight: 774.938
• UNII: 75C8DU40T0
• DSSTox Substance ID: DTXSID50870316
• Nikkaji Number: J1.964.346H
• Wikipedia: Ciluprevir
• Wikidata: Q5120036
• NCI Thesaurus Code: C76016
• Metabolomics Workbench ID: 144527
• ChEMBL ID: CHEMBL297884
• Mol file: 300832-84-2.mol

Synonyms:BILN 2061;BILN-2061;BILN2061

Chemical Property of Ciluprevir

Chemical Property:

• PKA: 3.32±0.60(Predicted)
• Density: 1.37g/cm³
• XLogP3: 6.4
• Hydrogen Bond Donor Count: 4
• Hydrogen Bond Acceptor Count: 12
• Rotatable Bond Count: 10
• Exact Mass: 774.34108375
• Heavy Atom Count: 55
• Complexity: 1420

Purity/Quality:

99% ^*data from raw suppliers

Ciluprevir 98+% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

Useful:

• Canonical SMILES: CC(C)NC1=NC(=CS1)C2=NC3=C(C=CC(=C3)OC)C(=C2)OC4CC5C(=O)NC6(CC6C=CCCCCCC(C(=O)N5C4)NC(=O)OC7CCCC7)C(=O)O
• Isomeric SMILES: CC(C)NC1=NC(=CS1)C2=NC3=C(C=CC(=C3)OC)C(=C2)O[C@@H]4C[C@H]5C(=O)N[C@@]6(C[C@H]6/C=C\CCCCC[C@@H](C(=O)N5C4)NC(=O)OC7CCCC7)C(=O)O
• Recent ClinicalTrials: Antiviral Efficacy, Pharmacokinetics and Safety of BILN 2061 ZW in Patients With Cirrhosis and Chronic Hepatitis C
• Uses: Treatment of Hepatitis C infection.

Technology Process of Ciluprevir

There total 54 articles about Ciluprevir 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%

(1S,4R,6S,7Z,14S,18R)-14-cyclopentyloxycarbonylamino-18-[2-(2-isopropylamino-thiazol-4-yl)-7-methoxy-quinolin-4-yloxy]-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acid methyl ester (681145-22-2) → ciluprevir (300832-84-2)

Guidance literature:

With lithium hydroxide; In tetrahydrofuran; methanol; water; at 20 ℃; for 15h;

DOI:10.1021/ol0489907

Reference yield: 80.0%

N-isopropyl-4-(7-methoxy-4-(phenylsulfonyl)quinolin-2-yl)thiazol-2-amine + C24H35N3O7 → ciluprevir (300832-84-2)

Guidance literature:

With potassium 3,7-dimethyloctan-3-olate; In n-heptane; N,N-dimethyl-formamide; at 20 ℃; for 0.75h;

DOI:10.1021/acs.joc.0c00554

Reference yield:

(2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid (13726-69-7,946610-68-0) → ciluprevir (300832-84-2)

Guidance literature:

Multi-step reaction with 9 steps

1: ethyldiisopropylamine; HOBt; EDC / acetonitrile / 1 h / 22 °C

2: triphenylphosphine; diisopropyl azodicarboxylate / tetrahydrofuran / 2 h / 20 °C

3: 19.4 g / HCl / dioxane / 1 h / 20 °C

4: ethyldiisopropylamine; TBTU / CH₂Cl₂ / 1.5 h / 20 °C

5: Hoveyda catalyst / CH₂Cl₂ / 24 h / 40 °C

6: lithium hydroxide / tetrahydrofuran; H₂O / 3 h / -5 - 0 °C

7: triethylamine; DMAP / CH₂Cl₂; toluene / 15 h / 20 °C

8: 10.7 g / Cs₂CO₃; 1-methyl-2-pyrrolidinone / 24 h / 50 °C

9: 90 percent / lithium hydroxide / tetrahydrofuran; H₂O / 8 h / 40 - 45 °C

With 1-methyl-pyrrolidin-2-one; hydrogenchloride; dmap; lithium hydroxide; di-isopropyl azodicarboxylate; benzotriazol-1-ol; caesium carbonate; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; triethylamine; N-ethyl-N,N-diisopropylamine; triphenylphosphine; dichloro(o-isporopoxyphenylmethylene)(triphenylphosphine)ruthenium(II); In tetrahydrofuran; 1,4-dioxane; dichloromethane; water; toluene; acetonitrile; 2: Mitsunobu reaction;

DOI:10.1021/jo060285j

upstream raw materials:

diazomethane

1-isopropylthiourea

(Z)-(1S,4R,6S,14S,18R)-14-Cyclopentyloxycarbonylamino-18-(7-methoxy-2-methoxycarbonyl-quinolin-4-yloxy)-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.0^4,6]nonadec-7-ene-4-carboxylic acid methyl ester

(1S,4R,6S,7Z,14S,18R)-14-cyclopentyloxycarbonylamino-18-[2-(2-isopropylamino-thiazol-4-yl)-7-methoxy-quinolin-4-yloxy]-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.0^4,6]nonadec-7-ene-4-carboxylic acid methyl ester

Refernces

• 1、 Liu, Dejun,Dong, Jingchao,Yin, Yunxing,Ma, Rujian,Shi, Yifeng,Wu, Hao,Chen, Shuhui,Li, Ge. "A concise synthesis of the HCV protease inhibitor BILN 2061 and its P3 modified analogs". . p. 1489 - 1502. Retrieved 2011/11/01.
• 2、 Faucher, Anne-Marie,Bailey, Murray D.,Beaulieu, Pierre L.,Brochu, Christian,Duceppe, Jean-Simon,Ferland, Jean-Marie,Ghiro, Elise,Gorys, Vida,Halmos, Ted,Kawai, Stephen H.,Poirier, Martin,Simoneau, Bruno,Tsantrizos, Youla S.,Llinas-Brunet, Montse. "Synthesis of BILN 2061, an HCV NS3 protease inhibitor with proven antiviral effect in humans". . p. 2901 - 2904. Retrieved 2007/10/03.