183004-94-6

Basic information

• Product Name: [(1S,2R)-1-Benzyl-2-hydroxy-3-[isobutyl-[(4-aminophenyl)sulfonyl]amino] propyl]-carbamic Acid tert-Butyl Ester
• Synonyms: [(1S,2R)-1-Benzyl-2-hydroxy-3-[isobutyl-[(4-aminophenyl)sulfonyl]amino] propyl]-carbamic Acid tert-Butyl Ester;[(1S,2R)-3-[[(4-Aminophenyl)sulfonyl](2-methylpropyl)amino]-2-hydroxy-1-(phenylmethyl)propyl]-carbamic Acid 1,1-Dimethylethyl Ester;CarbaMic acid, N-[(1S,2R)-3-[[(4-aMinophenyl)sulfonyl](2-Methylpropyl)aMino]-2-hydroxy-1-(phenylMethyl)propyl]-, 1,1-diMethylethyl ester;tert-Butyl ((2S,3R)-4-(4-amino-N-isobutylphenyl-sulfonamido)-3-hydroxy-1-phenylbutan-2-yl)carbama;tert-butyl ((2S,3R)-4-((4-amino-N-isobutylphenyl)sulfonamido)-3-hydroxy-1-phenylbutan-2-yl)carbamate;2-Methyl-2-Propanyl [(2S,3R)-4-{[(4-Aminophenyl)Sulfonyl](Isobutyl)Amino}-3-Hydroxy-1-Phenyl-2-Butanyl]Carbamate;tert-Butyl [(1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl]carbamate;tert-Butyl ((2S,3R)-4-(4-amino-N-isobutylphenyl-sulfonamido)-3-hydroxy-1-phenylbutan-2-yl)carb
• CAS NO: 183004-94-6
• Molecular Formula: C₂₅H₃₇N₃O₅S
• Molecular Weight: 491.65
• Product Categories: Chiral Reagents;Intermediates;Sulfur & Selenium Compounds
• Mol File: 183004-94-6.mol
• Article Data: 18

Chemical Properties

• Melting Point: 60-63 °C
• Appearance: /
• Density: 1.198 g/cm³
• Refractive Index: 1.571
• Storage Temp.: 2-8°C
• Solubility: Chloroform, Dichloromethane, Ethyl Acetate
• PKA: 11.98±0.46(Predicted)
• CAS DataBase Reference: [(1S,2R)-1-Benzyl-2-hydroxy-3-[isobutyl-[(4-aminophenyl)sulfonyl]amino] propyl]-carbamic Acid tert-Butyl Ester(CAS DataBase Reference)
• NIST Chemistry Reference: [(1S,2R)-1-Benzyl-2-hydroxy-3-[isobutyl-[(4-aminophenyl)sulfonyl]amino] propyl]-carbamic Acid tert-Butyl Ester(183004-94-6)
• EPA Substance Registry System: [(1S,2R)-1-Benzyl-2-hydroxy-3-[isobutyl-[(4-aminophenyl)sulfonyl]amino] propyl]-carbamic Acid tert-Butyl Ester(183004-94-6)

Safety Data

• Hazardous Substances Data: 183004-94-6(Hazardous Substances Data)

Usage

Chemical Properties

Off-White Solid

Uses

Darunavir intermediate, a potent inhibitor of HIV-1 protease

InChI:InChI=1/C25H37N3O5S/c1-18(2)16-28(34(31,32)21-13-11-20(26)12-14-21)17-23(29)22(15-19-9-7-6-8-10-19)27-24(30)33-25(3,4)5/h6-14,18,22-23,29H,15-17,26H2,1-5H3,(H,27,30)/t22-,23+/m0/s1

Upstream product

• 98760-08-8 (2R,3S)-3-[N-(tert-butyloxycarbonyl)amino]-1,2-epoxy-4-phenylbutane 
• 102123-74-0 (S)-tert-butyl (4-chloro-3-oxo-1-phenylbutan-2-yl)carbamate 
• 165727-45-7 tert-butyl ((2S,3S)-4-chloro-3-hydroxy-1-phenylbutan-2-yl)carbamate 
• 24939-24-0 4-aminobenzenesulfonyl chloride 
• 53668-36-3 4-amino-N-isobutylbenzenesulfonamide 
• 98760-08-8 (1-oxiranyl-2-phenylethyl)carbamic acid tert-butyl ester 
• 74651-77-7 2-(tert-butoxycarbonyloxyimino)-2-phenylacetonitrile 
• 169280-56-2 4-amino-N-(2R,3S)(3-amino-2-hydroxy-4-phenylbutyl)-N-isobutylbenzenesulfonamide 
• 159005-59-1 4-nitro-N-((2R(syn),3S)-3-(N-benzyloxycarbonylamino)-2-hydroxy-4-phenylbutyl)-N-isobutyl-benzenesulfonamide 
• 98-74-8 4-Nitrobenzenesulfonyl chloride 
• 143224-62-8 (2R,3S)-3-benzyloxycarbonylamino-2-hydroxy-1-(N-isobutylamino)-4-phenylbutane 
• 160232-08-6 (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol 
• 191226-98-9 [(1S,2R)-3-[(4-nitrophenylsulfonyl)(2-methylpropyl)amino]-2-hydroxy-1-(phenylmethyl)propyl]carbamic acid tert-butyl ester 
• 58632-95-4 2-(tert-Butoxycarbonyloxyimino)-2-phenylacetonitrile 

Downstream Products

• 1415750-61-6 [(1S,2R)-3-[(4-aminophenylsulfonyl)(2-methylpropyl)amino]-2-hydroxy-1-(phenylmethyl)propyl]amine hydrochloride 
• 635728-49-3 [14C]-Darunavir ethanolate 
• 183004-95-7 3-S-(N-t-butyloxyformamido)-2R-hydroxy-1-[(2-aminobenzothiazol-6-sulfonyl)(2-methylpropyl)amino]-4-phenylbutane 
• 206361-99-1 darunavir 
• 656236-05-4 N-{(1S,2R)-3-[(2-amino-benzothiazole-6-sulfonyl)-isobutyl-amino]-1-benzyl-2-hydroxypropyl}-2-(2,6-dimethyl-phenoxy)-acetamide 
• 656236-15-6 {(1S,2R)-3-[(2-amino-benzothiazole-6-sulfonyl)-isobutyl-amino]-1-benzyl-2-hydroxypropyl}-carbamic acid pyridin-3-ylmethyl ester 
• 656236-11-2 N-{(1S,2R)-3-[(2-amino-benzothiazole-6-sulfonyl)-isobutyl-amino]-1-benzyl-2-hydroxypropyl}-2-methyl-benzamide 
• 169280-61-9 carbamic acid, 2R-hydroxy-3-[[(2-aminobenzothiazol-6-yl)sulfonyl](2-methylpropyl)amino]-1S-(phenylmethyl)propyl-, phenylmethyl ester 
• 183004-96-8 N-[(1S,2R)-3-[(6-benzothiazolylsulfonyl)-(2-methylpropyl)amino]-2-hydroxy-1-(phenylmethyl)propyl]-carbamic acid-1,1-dimethylethyl ester 
• 656236-30-5 Benzothiazole-6-sulfonic acid ((2R,3S)-3-amino-2-hydroxy-4-phenyl-butyl)-isobutyl-amide 

Relevant articles and documents

An improved and robust scale-up process aided with identification and control of critical process impurities in darunavir ethanolate

A robust and safe industrial process, including five isolations and drying steps for widely prescribed anti-HIV (protease inhibitor) drug darunavir ethanolate 2, has been developed. A salient feature of this process is the development of procedures enabling the efficient synthesis of multi-kilogram quantity of darunavir ethanolate, and process demonstrations through plant scale preparation are offered where darunavir molecule has been prepared with overall > 70% chemical yield and > 99.8% purity without involving any purification procedure(s), with all possible process impurities below than the desired limit (not more than 0.08%) were isolated, synthesized and characterized. The developed process is entirely robust, very efficient and demonstrated up to kilograms scale.

PROCESS FOR THE PREPARATION OF SULFONAMIDES USEFUL AS RETROVIRAL PROTEASE INHIBITORS

The present invention relates to a process for the preparation of sulfonamides useful as retroviral protease inhibitors.

Discovery of imidazolidine-2,4-dione-linked HIV protease inhibitors with activity against lopinavir-resistant mutant HIV

A new series of HIV protease inhibitors has been designed and synthesized based on the combination of the (R)-(hydroxyethylamino)sulfonamide isostere and the cyclic urea component of lopinavir. The series was optimized by replacing the 6-membered cyclic urea linker with an imidazolidine-2,4-dione which readily underwent N-alkylation to incorporate various methylene-linked heterocycle groups that bind favorably in site 3 of HIV protease. Significant improvements compared to lopinavir were seen in cell culture activity versus wild-type virus (pNL4-3) and the lopinavir-resistant mutant virus A17 (generated by in vitro serial passage of HIV-1 (pNL4-3) in MT-4 cells). Select imidazolidine-2,4-dione containing PIs were also more effective at inhibiting highly resistant patient isolates Pt1 and Pt2 than lopinavir. Pharmacokinetic data collected for compounds in this series varied considerably when coadministered orally in the rat with an equal amount of ritonavir (5 mg/kg each). The AUC values ranged from 0.144 to 12.33 μg h/mL.