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Boceprevir InterMediates

Product Name
Boceprevir InterMediates
CAS No.
565456-77-1
Chemical Name
Boceprevir InterMediates
Synonyms
Methyl (1r,2s,5s)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylate;Methyl (1R,2S,5S)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylate hydrochloride;(1R,2S,5S)-Methyl 6,6-diMethyl-3-azabicyclo[3.1.0]hexane-2-carboxylate hydrochloride;(1R,2S,5S)-6,6-DIMETHYL-3-AZA-BICYCLO[3.1.0]HEXANE-2-CARBOXYLIC ACID METHYL ESTER HYDROCHLORIDE;(1R,2S,5S)-Methyl 6,6-diMethyl-3-azabicyclo[3.1.0]hexane-2-carboxylate;(1R,2S,5S)—6,6-DiMethyl-3-aza-bicylo[3.1.0]hexane-2-carboxylic acid Methyl ester hydrochloride;tert-butyl ((S)-1-cyano-2-((S)-2-oxopyrrolidin-3-yl)ethyl)carbamate;(1R,2S,5S)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylate hydrochloride;Boceprevir INT 1;Paxlovid Impurity 2
CBNumber
CB12466508
Molecular Formula
C9H16ClNO2
Formula Weight
205.68
MOL File
565456-77-1.mol
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Boceprevir InterMediates Property

storage temp. 
Inert atmosphere,Room Temperature
form 
solid
color 
Pale yellow
InChI
InChI=1/C9H15NO2.ClH/c1-9(2)5-4-10-7(6(5)9)8(11)12-3;/h5-7,10H,4H2,1-3H3;1H/t5-,6-,7-;/s3
InChIKey
FKVUDBWXNAFSPB-AUBOPKACNA-N
SMILES
C([C@H]1NC[C@@H]2C(C)(C)[C@H]12)(=O)OC.Cl |&1:1,4,8,r|
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Safety

HS Code 
2933998090
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Hazard and Precautionary Statements (GHS)

Symbol(GHS)
Signal word
Warning
Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H332Harmful if inhaled

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

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N-Bromosuccinimide Price

TRC
Product number
M342865
Product name
(1R,2S,5S)-Methyl6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylatehydrochloride
Packaging
10mg
Price
$60
Updated
2021/12/16
TRC
Product number
M342865
Product name
(1R,2S,5S)-Methyl6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylatehydrochloride
Packaging
50mg
Price
$75
Updated
2021/12/16
ChemScene
Product number
CS-B0867
Product name
3-Azabicyclo[3.1.0]hexane-2-carboxylicacid,6,6-dimethyl-,methylester,(Hydrochloride),(1R,2S,5S)-9CI
Purity
≥98.0%
Packaging
250mg
Price
$54
Updated
2021/12/16
Biosynth Carbosynth
Product number
FD22289
Product name
(1R,2S,5S)-6,6-Dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylic acid methyl ester hydrochloride
Packaging
500mg
Price
$70
Updated
2021/12/16
Apolloscientific
Product number
OR948553
Product name
Methyl(1R,2S,5S)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylatehydrochloride
Packaging
250mg
Price
$82
Updated
2021/12/16
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Boceprevir InterMediates Chemical Properties,Usage,Production

Uses

(1R, 2S, 5S)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylate methyl ester hydrochloride is the cost in the side chain synthesis of boceprevir the highest key intermediate.

Uses

(1S,2S,5R)-Methyl 6,6-diMethyl-3-azabicyclo[3.1.0]hexane-2-carboxylate hydrochloride is an azabicyclohexane derivative used in the preparation of hepatitis C virus (HCV) NS3 serine protease inhibitor.

General Description

Boceprevir is a peptidomimetic protease inhibitor with four moieties, P1–P3 and a Cap, where P1 is a racemic β-aminoamide, P2 is a chiral dimethylcyclopropylproline analog, P3 is (S)-tert-leucine, and Cap is a tert-butylcarbamoyl group. The 3-azabicyclo[3.1.0]hexane structure of P2 adopts a constrained conformation, so that the gem-dimethyl group has a fixed angle with respect to the bicyclic ring structure. The incorporation of the 3-azabicyclo[3.1.0]hexane moiety results in a 1000-fold increase in NS3 protease binding over proline in a pentapeptide scaffold. When boceprevir binds to the NS3 protease, the P2 moiety interacts with four amino acid residues at the active site. The starting material for the P2 moiety is the HCl salt of the dimethylcyclopropylproline methyl ester 2. For medicinal chemistry studies, it was prepared by cyclopropanation of a Δ3-pyrroline derivative of pyroglutamic acid.

Synthesis


The amine oxidation was carried out in a RC-1 Process Development Workstation (Mettler Toledo) equipped with pH feedback control and a gas induction impeller. A solution of 2.5 g MAON401(Codexis), 7.0 g catalase (Novozyme), and 0.1 g Antifoam 204 in 255 mL phosphate buffer (pH 7.0, 20 mM) was charged to the reactor. The temperature was set at 25°C, and 3 N NaOH was added to adjust the pH to 7.4. Pure oxygen (4 psig, or 207 mmHg) was applied to the enzyme solution prior to substrate addition. The substrate solution was prepared by dissolving 50 g NaHSO3 (0.45 mol) and 40 g 6 (0.36 mol) in 240 mL water. The substrate solution was charged to the enzyme solution over 19 h while maintaining the pH at 7.4 by titration of 3 N NaOH. By the end of the addition, 56.5 g of 3 N NaOH (0.15 mol) had been added to the reaction mixture, and conversion was 96.4%. For cyanation, CPME (240 mL) was added to the stream (compound 5 and 7) from enzymatic step. The solution was chilled to 10°C. A solution of NaCN in 70 mL water (22.9 g, 0.45 mol) was added over 0.5 h. The cyanation reached > 98% conversion after additional 0.5 h at 10°C. Significant protein precipitation took place when cyanide was added. The insoluble was removed by filtration through celite. After phase split, the aqueous phase was back extracted with 100 mL CPME. In methanolysis step, the CPME solution of 8 was added to HCl in MeOH (260 mL, [HCl] ≥ 6 N) at 5-10°C over 1 h. The solution was heated to 50°C and agitated for 4 h to complete the conversion. For product isolation, the volume was reduced to 160 mL by evaporation, followed by extraction under basic condition to give a solution of 9 in MTBE (375 mL). In the final step, the product was isolated by crystallization after forming the HCl salt. The MTBE solution was added to HCl in a mixture of 60 mL iPrOH and 240 mL MTBE at 0°C. The solution was seeded to crystallize for 5 h at -10°C. After solid isolation and drying under vacuum, 41.2 g (0.20 mol, 56% overall yield) of 2 was obtained in >98.5% purity and >99.9% e.e.

Boceprevir InterMediates Preparation Products And Raw materials

Raw materials

Preparation Products

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Boceprevir InterMediates Suppliers

Toronto Research Chemicals
Tel
--
Fax
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Email
info@trc-canada.com
Country
Canada
ProdList
6038
Advantage
71
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View Lastest Price from Boceprevir InterMediates manufacturers

Hebei Yanxi Chemical Co., Ltd.
Product
Boceprevir InterMediates 565456-77-1
Price
US $0.00/kg
Min. Order
1kg
Purity
0.99
Supply Ability
20tons
Release date
2023-10-08
PNP Biotech Co. Ltd
Product
(1R,2S,5S)-methyl 6,6-dimethyl-3-aza-bicyclo[3.1.0]hexane-2-carboxylate hydrochloride 565456-77-1
Price
US $0.00/kg
Min. Order
25kg
Purity
98%
Supply Ability
Inquiry
Release date
2022-10-20
Wuhan Boye Science And Technology Development Co., Ltd.
Product
(1r,2s,5s)-6,6-Dimethyl-3-Aza-Bicyclo[3.1.0]Hexane-2-Carboxylic Acid Methyl Ester Hydrochloride 565456-77-1
Price
US $0.00/Kg/Bag
Min. Order
1Kg/Bag
Purity
98%
Supply Ability
1 ton
Release date
2021-12-09

565456-77-1, Boceprevir InterMediatesRelated Search:


  • (1R,2S,5S)—6,6-DiMethyl-3-aza-bicylo[3.1.0]hexane-2-carboxylic acid Methyl ester hydrochloride
  • Boceprevir InterMediates
  • Methyl (1R,2S,5S)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylate hydrochloride
  • (1R,2S,5S)-Methyl 6,6-diMethyl-3-azabicyclo[3.1.0]hexane-2-carboxylate hydrochloride
  • 3-Azabicyclo[3.1.0]hexane-2-carboxylic acid, 6,6-diMethyl-, Methyl ester, (Hydrochloride), (1R,2S,5S)- (9CI)
  • (1S,2S,5R)-Methyl 6,6-diMethyl-3-azabicyclo[3.1.0]hexane-2-carboxylate hydrochloride
  • 3-Azabicyclo[3.1.0]hexane-2-carboxylic acid, 6,6-diMethyl-, Methyl ester, hydrochloride, (1R,2S,5S)-
  • Methyl (1r,2s,5s)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylate
  • (1R,2S,5S)-Methyl 6,6-diMethyl-3-azabicyclo[3.1.0]hexane-2-carboxylate
  • 3-Azabicyclo[3.1.0]hexane-2-carboxylicacid,6,6-diMethyl-,Methylester,hydrochloride(1:1),(1R,2S,5S)-
  • (1R,2S,5S)-6,6-Dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylic acid methyl ester HCl
  • 1.3-Azabicyclo[3.1.0]hexane-2-carboxylic acid, 6,6-dimethyl-, methyl ester, hydrochloride(1R,2S,5S)
  • Boceprevir INT 1
  • (1R,2S,5S)-6,6-DIMETHYL-3-AZA-BICYCLO[3.1.0]HEXANE-2-CARBOXYLIC ACID METHYL ESTER HYDROCHLORIDE
  • 5S)-6
  • 6-DIMETHYL-3-AZA-BICYCLO[3.1.0]HEXANE-2-CARBOXYLIC ACID METHYL ESTER HYDROCHLORIDE
  • PF-07321332 intermediate
  • (1R,2S,5S)-6,6-DIMETHYL-3-AZA-BICYCLO[3.1.0]HEXANE-2-CARBOXYLIC ACID METHYL ESTER HYDROCHLORID
  • tert-butyl ((S)-1-cyano-2-((S)-2-oxopyrrolidin-3-yl)ethyl)carbamate
  • Paxlovid Int.
  • PF-07321332-002
  • (1R,2S,5S)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylate hydrochloride
  • (1R,2S,5S)-Methyl 6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylate HCl
  • (1R,2S,5S)-methyl 6,6-dimethyl-3-aza-bicyclo[3.1.0]hexane-2-carboxylate hydrochlorid
  • (1R,2S,5S)-methyl 6,6-dimethyl-3-aza-bicyclo[3.1.0]hexane-2-...
  • (1R,2S,5S)-6,6-Dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylate acid Methyl ester hydrochloridee
  • Paxlovid Impurity 2
  • Nirmatrelvir intermediate 565456-77-1
  • Nirmatrelvir Intermediate
  • (1R.28,5S)-6,6-DIMETHYL-3-AZA-BICYCLO[3.1.0]HEXANE-2- CARBOXYLICACID METHYL ESTER HYDRoCHLORIDE
  • Paxlovid Intermediate 2
  • (1R,2S,5S)-6,6-dimethyl-3-aza-bicylo[3.1]hexane-2-carboxylic acid methyl ester hydrochloride
  • 3-Azabicyclo[3.1.0]hexane-2-carboxylic acid, 6,6-dimethyl-, methyl ester, hydrochloride (1:1), (1R,2S,5S)- (ACI)
  • Paxlovid Interediate
  • Intermediate of Boprevir
  • PF-07321332 Impurity 1
  • 6,6-Dimethyl-3-aza-bicyclo[3.1.0]hexane-2-carboxylic acid methyl ester hydrochloride
  • Methyl (1S,2S,5R)-1,5,6,6-tetramethyl-3-azabicyclo[3.1.0]hexane-2-carboxylate
  • Nirmatrelvir Impurity 10 HCl
  • Nirmatrelvir Impurity 29 HCl
  • 565456-77-1
  • Boceprevir intermediate
  • Chiral Reagents
  • Heterocycles
  • Intermediates & Fine Chemicals
  • Pharmaceuticals
  • 565456-77-1