Beclabuvir
- Product Name
- Beclabuvir
- CAS No.
- 958002-33-0
- Chemical Name
- Beclabuvir
- Synonyms
- Beclabuvir;Beclabuvir(BMS-791325);(1aR,12bS)-8-cyclohexyl-N-[(dimethylamino)sulfonyl]-1,1a,2,12b-tetrahydro-11-methoxy-1a-[(3-methyl-3,8-diazabicyclo[3.2.1]oct-8-yl)carbonyl]-cycloprop[d]indolo[2,1-a][2]benzazepine-5-carboxamide;Cycloprop[d]indolo[2,1-a][2]benzazepine-9-carboxamide, 12-cyclohexyl-N-[(dimethylamino)sulfonyl]-4b,5,5a,6-tetrahydro-3-methoxy-5a-[(3-methyl-3,8-diazabicyclo[3.2.1]oct-8-yl)carbonyl]-, (4bS,5aR)-
- CBNumber
- CB12717749
- Molecular Formula
- C36H45N5O5S
- Formula Weight
- 659.84
- MOL File
- 958002-33-0.mol
Beclabuvir Property
- Density
- 1.45±0.1 g/cm3(Predicted)
- storage temp.
- Store at -20°C
- solubility
- DMSO:30.0(Max Conc. mg/mL);45.46(Max Conc. mM)
- form
- Solid
- pka
- 4.44±0.40(Predicted)
- color
- White to off-white
N-Bromosuccinimide Price
- Product number
- CS-6041
- Product name
- Beclabuvir
- Purity
- 99.91%
- Packaging
- 1mg
- Price
- $168
- Updated
- 2021/12/16
- Product number
- CS-6041
- Product name
- Beclabuvir
- Purity
- 99.91%
- Packaging
- 5mg
- Price
- $420
- Updated
- 2021/12/16
- Product number
- CS-6041
- Product name
- Beclabuvir
- Purity
- 99.91%
- Packaging
- 10mg
- Price
- $660
- Updated
- 2021/12/16
- Product number
- CS-6041
- Product name
- Beclabuvir
- Purity
- 99.91%
- Packaging
- 50mg
- Price
- $1920
- Updated
- 2021/12/16
Beclabuvir Chemical Properties,Usage,Production
Description
Beclabuvir is a non-nucleoside, nonstructural protein 5B (NS5B) polymerase inhibitor approved in Japan as part of a fixed-dose combination product for the treatment of hepatitis C virus (HCV). Upon administration and after intracellular uptake, the drug binds to the allosteric, noncatalytic “Thumb 1” site of NS5B resulting in a decreased rate of viral RNA synthesis and replication.4 Beclabuvir is combined with asunaprevir and declatasvir (both approved in 2014) and was discovered and developed by Bristol-Myers Squibb.
Synthesis
The syntheses of asunaprevir and declatasvir were described
in an earlier review article.Condensation of
indole-6-carboxylic acid (1) with cyclohexanone under basic
conditions gave acid 2 in quantitative yield. Hydrogenation of
the double bond in 2 using Pearlman?ˉs catalyst was followed by
esterification to give ester 3 in high yield. Bromination of the
indole at the 2-position was accomplished with pyridinium
tribromide, and this was followed by saponification to provide
acid 4. Treatment of 4 with carbonyldiimidazole (CDI)
followed by N,N- dimethylsulfamide and 1, 8 -
diazabicyclo[5.4.0]undec-7-ene (DBU) gave compound 5 in
74% yield. Suzuki coupling of 5 with commercial boronic acid 6
provided intermediate 7, which converted to hemiaminal 8
upon continued heating in 61% yield. Compound 8 was then
treated with methyl 2-(dimethoxyphosphoryl)acrylate (9) to
affect a tandem conjugate addition and Horner?Wadsworth?
Emmons (HWE) olefination to give ester 10. Alternatively, the
Suzuki coupling reaction of 5 with 6 could be stopped at
intermediate 7, which could be treated with 9 to promote the tandem conjugate addition/HWE to give 10. Corey?-Chaykovsky cyclopropanation of 10 using sodium hydride
and trimethylsulfoxonium iodide followed by chiral separation
provided cyclopropane 11 in good yield and >99% enantiomeric
excess (ee). Saponification of the methyl ester of 11
followed by coupling with 3-methyl-3,8-diazabicyclo[3.2.1]-
octane dihydrochloride (12) gave beclabuvir (I) in high yield.