4-Amino-N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-isobutylbenzene-1-sulfonamide

• CAS: 169280-56-2
• Catalog Number: ACM169280562
• Category: Main Products
• Molecular Weight: 391.53
• Molecular Formula: C₂₀H₂₉N₃O₃S
• Synonyms: 4-AMINO-N-[(2R,3S)-3-AMINO-2-HYDROXY-4-PHENYLBUTYL]-N-ISOBUTYLBENZENE-1-SULFONAMIDE;4-Amino-N-((2R,3S)-3-amino-2-hydroxy-4-phenylbutyl)-N-isobutylbenzenesulfonamide;4-Amino-N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-(2-methylpropyl)benzenesulfonamide;BenzenesulfonaMide, 4-aMino-N-[(2R,3S)-3-aMino-2-hydroxy-4-phenylbutyl]-N-(2-Methylpropyl)-;(2R,3S)-N-(3-AMINO-2-HYDROXY-4-PHENYLBUTYL)-N-ISOBUTYL-4-AMINO-BENZENESULFONAMIDE;4-amino-N-(3-amino-2-hydroxy-4-phenylbutyl)benzenesulfonamide
• IUPAC Name: 4-amino-N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-(2-methylpropyl)...
• Boiling Point: 609.105ºC at 760 mmHg
• Flash Point: 322.175ºC
• Density: 1.226 g/cm³
• Exact Mass: 391.19300

Case Study

4-Amino-N-((2R,3S)-3-Amino-2-Hydroxy-4-Phenylbutyl)-N-Isobutylbenzenesulfonamide for the Synthesis of HIV-1 PR/RT Dual Inhibitors

Zhu, Mei, et al. European journal of medicinal chemistry, 2021, 220, 113498.

The study developed and tested a novel class of HIV-1 PR/RT dual inhibitors through analysis of potential ligand binding site interactions combined with consistent key active site residues. The introduction of cinnamic acid and phenylpropionic acid with flexible molecular chains and reduced steric hindrance resulted in enhanced inhibitory action against HIV-1 RT for this inhibitor class. The synthetic process began with 4-Amino-N-((2R, 3S)-3-amino-2-hydroxy-4-phenylbutyl)-N-isobutylbenzenesulfonamide (23) can produce a series of compounds including 35b~40b.
General synthetic procedures
· Compounds 35b-40b synthesis from 4-amino-N-((2R,3S)-3-amino-2-hydroxy-4-phenylbutyl)-N-isobutylbenzenesulfonamide (23) requires conducting an EDCI/HOBt/DMAP-mediated coupling reaction under argon conditions.
· The synthesis of each target compound involves reacting 23 with either an acrylamide or propanamide precursor (29-34) in dry DMF at 0°C before increasing the temperature to 25°C.
· Following the sequential addition of EDCI (1.5 mmol), HOBt (1.1 mmol), and DMAP (0.2 mmol) the reaction mixture undergoes stirring for 10 minutes at 0°C before stirring at 25°C for 1 hour after EDCI/HOBt addition and proceeding with 2 hours of stirring after adding DMAP.
· After solvent removal under reduced pressure the residue gets water dilution then undergoes extraction with CH2Cl2 drying over Na2SO4 followed by purification through silica gel column chromatography using 5% CH3OH in CH2Cl2 as the eluent.
· The protocol produces final compounds (35b-40b) as white amorphous solids with yields between 75% and 81% based on the specific acrylamide/propanamide precursor utilized.

4-Amino-N-((2R,3S)-3-Amino-2-Hydroxy-4-Phenylbutyl)-N-Isobutylbenzenesulfonamide for the Synthesis of Darunavir

Gary L. Moore, et al. Org. Process Res. Dev. 2017, 21(1), 98-106.

This work described a practical method for the synthesis of a key intermediate in the synthesis of darunavir starting from monopotassium isocitrate. The last step of this synthetic route involves coupling the obtained carbonate 8 with 4-amino-N-((2R,3S)-3-amino-2-hydroxy-4-phenylbutyl)-N-isobutylbenzenesulfonamide to provide the darunavir drug substance in the form of an unsolvate.
Synthetic route of darunavir
· 4-Amino-N-((2R,3S)-3-amino-2-hydroxy-4-phenylbutyl)-N-isobutylbenzenesulfonamide (391.5 mg, 1.00 mmol) and 2,5-dioxopyrrolidin-1-yl((3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl)carbonate (8) (271.2 mg, 1.00 mmol) were mixed in acetonitrile (10 mL) at room temperature.
· Triethylamine (101 mg, 1.00 mmol) was added, and the mixture was stirred for 16 hours. The solution was concentrated under 40-50 Torr and then diluted with MTBE (40 mL). It was subsequently washed with 10% aqueous Na2CO3 (20 mL), 10% aqueous H2SO4 (20 mL), and another 10% aqueous Na2CO3 (20 mL). After concentration under 40-50 Torr, a white foam was obtained. This foam was dissolved in ethanol (3 mL) and heated to reflux before cooling to room temperature, which allowed solid to precipitate.
· The resultant mixture was stirred for another 16 hours, and the white solid was then collected by filtration. The final yield of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl ((2S,3R)-4-((4-amino-N-isobutylphenyl)sulfonamido)-3-hydroxy-1-phenylbutan-2-yl)carbamate (darunavir) was 414 mg, corresponding to a 76% yield with an HPLC purity of 99.2%.