229975-97-7

Basic information

• Product Name: Atazanavir sulfate
• Synonyms: 1-(4-Biphenylyl)-4(S)-hydroxy-5(S)-2,5-bis{[N-(methoxycarbonyl-)-L-tert-leucinyl]amino}-6-phenyl-2-azahexane;Aids060276;Aids-060276;Cgp 75355;Methyl N-[(1S)-1-{[(2S,3S)-3-hydroxy-4-[(2S)-2-[(Methoxycarbonyl)aMino]-3,3-diMethyl-N'-{[4-(pyridin-2-yl)phenyl]Methyl}butanehydrazido]-1-phenylbutan-2-yl]carbaMoyl}-2,2-diMethylpropyl]carbaMate;Atazanavir sulfate (BMS-232632-05);BMS-232632-05;Zrivada
• CAS NO: 229975-97-7
• Molecular Formula: C38H52N6O7.H2SO4
• Molecular Weight: 802.93
• EINECS: 1312995-182-4
• Product Categories: Atazanavir;Inhibitor;peptides;BMS-232632-05, Reyataz;Inhibitors;Antiviral Agents
• Mol File: 229975-97-7.mol

Chemical Properties

• Melting Point: 195.0°, or acetone; mp 198-199° (dec)
• Boiling Point: 995.5 °C at 760 mmHg
• Flash Point: 555.8 °C
• Appearance: /
• Density: 1.164g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Solubility: ≥28.7 mg/mL in DMSO with gentle warming; insoluble in H2O; ≥4.05 mg/mL in EtOH with gentle warming and ultrasonic
• CAS DataBase Reference: Atazanavir sulfate(CAS DataBase Reference)
• NIST Chemistry Reference: Atazanavir sulfate(229975-97-7)
• EPA Substance Registry System: Atazanavir sulfate(229975-97-7)

Safety Data

• Safety Statements: 24/25
• Hazardous Substances Data: 229975-97-7(Hazardous Substances Data)

Usage

Uses

1. Used in Pharmaceutical Industry:
Atazanavir sulfate is used as an antiviral agent for the treatment of HIV infection. It functions as an HIV protease inhibitor, preventing the replication of the virus and thus helping to manage the progression of the disease in patients.
2. Used in Research and Development:
Atazanavir sulfate serves as an intermediate in the development of novel HIV protease inhibitors. Its chemical properties and antiviral activity make it a valuable compound for further research and the creation of new drugs to combat HIV.

Synthesis

The synthesis of atazanavir (III) appeared in several reports. The synthetic route depicted in the scheme was one of the best routes which was suitable for large scale production. The commercially available chiral diol 25 was converted to its silyl mesylate 26 in one pot via selective silylation and subsequent mesylation. This oily intermediate 26 was carried into the next step without further purification. The desilylation of 26 was achieved by using inexpensive ammonium fluoride. The resulting solid product 27 was readily isolated and further purified through recrystallization from IPA/H2O in 80% yield. The epoxide formation from 27 was affected by KOtBu in THF/IPA to provide enantiomerically pure epoxide 28 in 88% yield. Suzuki coupling of boronic acid 29 with bromopyridine (30) provided pyridyl benzaldehyde 31 in 80% yield after crystallization. The subsequent condensation of aldehyde 31 with t-butylcarbamate was carried out by refluxing in toluene/IPA and Shiff base 32 was collected by filtration upon cooling. Reduction of hydrazone 32 to hydrazine 33 was accomplished by employing a catalytic phase-transfer hydrogenation protocol (Pd/C, HCOONa) to furnish hydrazine 33 in 78% yield after crystallization. Coupling of the hydrazinocarbamate 33 with epoxide 28 was performed in refluxing IPA, followed by the addition of water to precipitate the crude product. Subsequent recrystallization from MeCN/H2O furnished 34 in 85% yield. Treatment of 34 with concentrated HCl in THF at 50oC removed the two Boc groups in 34 to give the product as an oil, which was then dissolved in a mixture of DCM/DIPEA and slowly transferred into a premixed solution of N-methoxycarbonyl- L-tert-leucine (35), HOBT, and WSC in DCM. After removal of the solvent the crude product was crystallized from IPA/EtOH to furnish the freebase 36 in 82% yield. The sulfate III was obtained by stirring the free base 36 with concentrated H2SO4 in EtOH at ambient temperature. Direct crystallization by addition of n-heptane provided the sulfate salt III as an easily filterable solid in 85% yield.

InChI:InChI=1/C38H52N6O7.H2O4S/c1-37(2,3)31(41-35(48)50-7)33(46)40-29(22-25-14-10-9-11-15-25)30(45)24-44(43-34(47)32(38(4,5)6)42-36(49)51-8)23-26-17-19-27(20-18-26)28-16-12-13-21-39-28;1-5(2,3)4/h9-21,29-32,45H,22-24H2,1-8H3,(H,40,46)(H,41,48)(H,42,49)(H,43,47);(H2,1,2,3,4)/t29-,30-,31+,32+;/m0./s1

Upstream product

• 198904-31-3 atazanavir 
• 20859-02-3 L-tert-Leucine 
• 149451-80-9 (2S,3S)-3-(t-butoxycarbonylamino)-4-phenylbutane-1,2-diol 
• 437713-03-6 methanesulfonic acid 2-tert-butoxycarbonylamino-1-(tert-butyl-dimethyl-silanyloxymethyl)-3-phenyl-propyl ester 
• 87199-17-5 4-formylphenylboronic acid, 
• 98760-08-8 (2R,3S)-3-[N-(tert-butyloxycarbonyl)amino]-1,2-epoxy-4-phenylbutane 
• 198904-86-8 1-[4-(pyridine-2-yl)phenyl]-5(S)-2,5-bis[(tert-butyloxycarbonyl)amino]-4(S)-hydroxy-6-phenyl-2-azahexane 
• 109-04-6 2-bromo-pyridine 
• 162537-11-3 (S)-2-(methoxycarbonylamino)-3,3-dimethylbutanoic acid 
• 198904-87-9 1-[4-(pyridin-2-yl)phenyl]-4(S)-hydroxy-5(S)-2,5-diamino-6-phenyl-2-azahexane trihydrochloride 
• 127406-56-8 4-(2'-pyridyl)benzaldehyde 
• 198904-84-6 2-[4-(2-pyridinyl)phenyl]methylenehydrazinecarboxylic acid tert-butyl ester 
• 198904-85-7 N-1-(tert-butoxycarbonyl)-N-2-[4-(pyridine-2-yl)benzyl]hydrazine 
• 369362-96-9 (2S,3R)-2-amino-4-chloro-1-phenylbutan-3-ol hydrochloride 

Relevant articles and documents

A process for preparing A [...] sulfate method

A disclosed method for preparing A type atazanavir sulfate comprises the following steps: step a) adding atazanavir free alkali into an organic solvent to prepare a transparent solution at a controlled temperature of 10-65 DEG C, wherein the organic solve

TABLETED COMPOSITIONS CONTAINING ATAZANAVIR

Disclosed are compressed tablets containing atazanavir sulfate, optionally with another active agents, e.g., anti-HIV agents, granules that contain atazanavir sulfate and an intragranular lubricant that can be used to make the tablets, compositions comprising a plurality of the granules, processes for making the granules and tablets, and methods of treating HIV.

A process for preparing a sulfuric acid Atazanavir method (by machine translation)

A is applied to the technical field of drug synthesis in the puma monomer as the raw material to prepare sulfuric acid Atazanavir method, the preparation method comprises the following steps: the puma monomer uses ethanol to dissolve after the dilution, t

A atazanavir bisulfate method for preparing A-type crystallization (by machine translation)

The invention discloses a atazanavir bisulfate method for preparing A-type crystallization, comprising the following steps: a) the application of the free base in ethanol, stir at room temperature, then dropping concentrated sulfuric acid, the reaction liquid heating and stirring, and then to add inert solvent, cooling crystallization, filtration and dried to obtain application E-type crystallization ethanol composition; wherein the molar concentration of the concentrated sulfuric acid is preferably 15-18.4mol/L; b) step 1) ethanol compound is obtained in the acetone E-type crystallization, heating to reflux stirring, cooling, filtering, and dried to obtain atazanavir bisulfate A-type crystallization. Preparation method of the invention aims of the invention, the operability of the process, improved product appearance property, improve the quality and purity of the product. (by machine translation)

PROCESS FOR THE PREPARATION OF ATAZANAVIR BISULFATE

The present invention relates to an improved process for the preparation of Atazanavir bisulfate Form A. The present invention also relates to a pharmaceutical composition using the Atazanavir bisulfate Form A of the invention.

PROCESS FOR PREPARING ATAZANAVIR SULPHATE

The present invention relates to a process for the preparation of Compound (A): (Formula (A)) wherein the process comprises contacting atazanavir base (Compound (II)) with sulphuric acid in a combination of two or more solvents and isolating compound (A).

PROCESS FOR THE PREPARATION OF ATAZANAVIR OR ITS BISULFATE SALT

The present invention relates to an improved process for the preparation of atazanavir bisulfate, an inhibitor of retroviral aspartate protease. The process of the present invention comprises conversion of 1,1-dimethylethyl[(2S,3R)-4-chloro-3-hydroxy-phenylbutan-2-yl]carbamate (Formula II) into 1-[4-(pyridine-2-yl)-phenyl]-4(S)-5 hydroxy-2-N-tert-butoxycarbonylamino-5(S)—N—(N-methoxycarbonyl-(L)-tert-leucyl)amino-6-phenyl-2-azahexane (Formula VII) without isolating intermediate compounds formed therein, followed by its subsequent conversion to atazanavir or its bisulfate salt.

Process for Preparing Form A of Atazanavir Sulfate

A process of making Form A of atazanavir sulfate comprises: a) mixing atazanavir free base with a solvent selected from the group consisting of methanol (MeOH), ethanol (EtOH), isopropanol (IPA), N-methylprrolidone (NMP) and combinations thereof; b) react

PROCESS FOR PREPARATION OF ATAZANAVIR OR ITS BISULFATE SALT

The present invention relates to an improved process for the preparation of atazanavir bisulfate, an inhibitor of retroviral aspartate protease. The process of the present invention comprises conversion of 1,1-dimethylethyl[(2S,3R)-4-chloro-3-hydroxy- -phenylbutan-2-yl]carbamate (Formula II) into 1-[4-(pyridine-2-yl)-phenyl]-4(S)-5 hydroxy-2-N-tert-butoxycarbonylamino-5(S)-N-(N-methoxycarbonyl-(L)-tert- leucyl)amino-6-phenyl-2-azahexane (Formula VII) without isolating intermediate compounds formed therein, followed by its subsequent conversion to atazanavir or its bisulfate salt.

PROCESS FOR THE PREPARATION OF ATAZANAVIR SULFATE SUBSTANTIALLY FREE OF DIASTEREOMERS

The present invention provides atazanavir sulfate substantially free of diastereomeric impurities. The present invention also provides atazanavir sulfate having D-tertiary leucine analogues less than 0.1%. The present invention further relates to an improved process for preparing atazanavir sulfate, substantially free of its diastereoisomeric impurities, which comprises of reacting diamino compound (IV) with N-methoxycarbonyl-(L)-tertiary-leucine (V) having D-isomer less than 0.1 % to obtain atazanavir base; conversion of atazanavir base to atazanavir sulfate by reacting with sulfuric acid and crystallization of atazanavir sulfate from suitable organic solvent(s).