85743-99-3

Upstream product

• 26661-13-2 N₄-benzoylcitosine 
• 999-97-3 1,1,1,3,3,3-hexamethyl-disilazane 
• 26661-13-2 4-N-benzoylcytosine 
• 10416-59-8 N,O-Bis(trimethylsilyl)acetamide 
• 27607-77-8 trimethylsilyl trifluoromethanesulfonate 
• 26661-13-2 N⁴-Benzoylcytosine 
• 10416-59-8 N,O-bis-(trimethylsilyl)-acetamide 

Downstream Products

• 23624-64-8 N⁴-benzoyl-1-(2’,3’,5’-tri-O-benzoyl-β-D-ribofuranosyl)-cytosine 
• 31652-74-1 2',3',5'-tri-O-benzoyl-L-cytidine 
• 161469-38-1 N⁴-Benzoyl-1-(1,3-dioxolan-2-yl)cytosine 
• 162934-38-5 <4'-O-(p-Nitrobenzoyl)-2',3'-dideoxy-β-D-glycero-pent-2'-enopyranosyl>-N⁴-benzoylcytosine 
• 162934-39-6 <4'-O-(p-Nitrobenzoyl)-2',3'-dideoxy-α-D-glycero-pent-2'-enopyranosyl>-N⁴-benzoylcytosine 
• 959366-66-6 N-[1-((2R,4R)-2-Benzyloxymethyl-2-methyl-[1,3]dioxolan-4-yl)-2-oxo-1,2-dihydro-pyrimidin-4-yl]-benzamide 
• 959324-92-6 N-[1-((2S,4S)-2-Benzyloxymethyl-2-methyl-[1,3]dioxolan-4-yl)-2-oxo-1,2-dihydro-pyrimidin-4-yl]-benzamide 
• 959366-61-1 N-[1-((2S,4R)-2-Benzyloxymethyl-2-methyl-[1,3]dioxolan-4-yl)-2-oxo-1,2-dihydro-pyrimidin-4-yl]-benzamide 
• 479035-82-0 N⁴-benzoyl-1-(5-O-benzoyl-2,3-dideoxy-3,3-difluoro-β-D-ribofuranosyl)cytosine 
• 698391-73-0 N⁴-benzoyl-1-(5-O-benzoyl-2,3-dideoxy-3,3-difluoro-α-D-ribofuranosyl)cytosine 

Relevant academic research and scientific papers

Synthesis and biological evaluation of deuterated sofosbuvir analogs as HCV NS5B inhibitors with enhanced pharmacokinetic properties

A series of deuterated sofosbuvir analogs were designed and prepared with the aim of improving their pharmacokinetic properties. The devised synthetic routes allow for site-selective deuterium incorporation with high levels of isotopic purity. As expected, the deuterated analogs (37-44) are as efficacious as sofosbuvir when tested in vitro inhibition of viral replication (replicon) assays. Compared with sofosbuvir, deuterated analog 40 displays improved in vivo pharmacokinetics profiles in rats and dogs in terms of the metabolite and the prodrug. The Cmax and area under the curve (AUC) of 40 in dogs were increased by 3.4- and 2.7-fold, respectively. Due to the enhanced pharmacokinetic properties and the great synthetic advantage of an inexpensive deuterium source (D2O) for 40, it was chosen for further investigation.

A key intermediate for the preparation of rope non-cloth wei (by machine translation)

The invention relates to a kind of the formula (I): As shown by a rope non-cloth wei key intermediate of the preparation method, the present invention in order to compound 3, 5 - dibenzoyl - 2 - deoxy - 2 - fluoro - 2 methyl - D - ribose - γ - lactone as

Stereoselective Synthesis of Sofosbuvir through Nucleoside Phosphorylation Controlled by Kinetic Resolution

The preparation of Sofosbuvir, the potent key component of recent Hepatitis C (HCV) infection therapies, is reported. The process is based on the dynamic kinetic resolution of the stereochemically unstable isopropyl-2-{[chloro(phenoxy)phosphoryl]-amino}propanoate (8). A high stereoselectivity was obtained when the right protective group for 3′-OH was chosen. Ester and carbonate-based protective groups gave lower stereoselectivities, but benzyl protection allowed the phosphorylation to occur with a 92:8 ratio in favour of the product with the right configuration at the P-stereogenic centre. Starting from the γ-lactone of 2-deoxy-2-fluoro-2-methylpentonic acid, the synthesis was accomplished in eight steps in 40 % overall yield using commercially available reagents, and without any enzymatic or chemical resolution technique.

Β-selective D-psicofuranosylation of pyrimidine bases and thiols

N-Glycosidation of D-psicofuranosyl donor 1 with pyrimidine bases took place β-selectively in a β/α-ratio of 8:1 ~ 7:1. For S-glycosidation, 3,4-O-(3-pentylidene)-protected D-psicofuranosyl donor 15 was effective to increase β-selectivity up to 7:1.

Intermediate compound for synthesis of sofosbuvir and synthetic method thereof

The invention discloses an intermediate compound for synthesis of sofosbuvir and a synthetic method thereof; the intermediate compound comprises 4 intermediate products and 1 target compound, wherein the 4 intermediate products include methyl ((2R,3R,4R)-3-(benzoyloxy)-4-fluoro-5-hydroxy-4-methyltetrahydrofuran-2-yl) benzoate, methyl ((2R,3R,4R)-3-(benzoyloxy)-4-fluoro-5-chloro-4-methyltetrahydrofuran-2-yl) benzoate, (2'R)-N-benzoyl-2'-deoxy-2'-fluoro-2'-methylcytidine 3',5'-dibenzoate, and ((2R,3R,4R,5R)-3-(benzoyloxy)-4-fluoro-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-methyltetrahydrofuran-2-yl) methyl benzoic acid, and the target compound is (2'R)-2'-deoxy-2'-fluoro-2'-methylcytidine. Compared with existing synthetic methods, the synthetic method has high content of target compound and has little impurities generated in the synthetic process; the results of the synthetic method are stable, the synthetic method is simple to perform and is applicable to large-scale industrial production and technical popularization.

Bridged ring fluoroester, and preparation method and application thereof

The invention discloses fire-new bridged ring fluoroester (1R,4R,5R,6R)-6-fluoro-6-methyl-2,7-dioxygen bicyclo [2.2.1] heptyl-5-formic ether (the structural formula is shown as a formula V), a preparation method of the bridged ring fluoroester, and application of the bridged ring fluoroester to synthesis of PSI-6130 by using the compound V for further synthesis of sofosbuvir. The structure is in the specification. The fire-new bridged ring fluoroester has the advantages that the synthesis path is simple and short; the three-dimensional configuration selectivity is excellent and controllable; heavy metal and virulent raw materials are not used in the reaction process; few three wastes are generated; the environment-friendly effect is achieved; the obvious economic benefits are realized; the fire-new bridged ring fluoroester is suitable for industrial mass production.

PROCESS FOR THE PREPARATION OF SOFOSBUVIR

A process for the preparation of intermediates 9, useful in the synthesis of sofosbuvir, as well as intermediates of formula [12] are disclosed herein.

Deuterated nucleoside derivative

The present invention relates to deuterated nucleoside derivative, particularly to a compound having a structure represented by a formula I or a pharmaceutically acceptable salt thereof. According to the present invention, the compound represented by the formula I has excellent pharmacokinetic properties and is expected to reduce the clinical dose so as to reduce the treatment and benefit more patients. The formula I is defined in the specification.

PROCESS FOR THE PREPARATION OF 2-DEOXY-2-FLUORO-2-METHYL-D-RIBOFURANOSYL NUCLEOSIDE COMPOUNDS

An improved process for the preparation of (2'R)-2'-deoxy-2'-fluoro-2'-methylcytidine derivatives of formula I, (I), wherein R1 is selected from C1-4-alkyl is described. The (2'R)-2'-deoxy-2'-fluoro-2'-methylcytidine derivatives of formula I have the potential to be useful as prodrugs for potent inhibitors of the Hepatitis C Virus (HCV) NS5B polymerase.

PROCESS FOR THE PREPARATION OF 2-DEOXY-2-FLUORO-2-METHYL-D-RIBOFURANOSYL NUCLEOSIDE COMPOUNDS

An improved process for the preparation of (2′R)-2′-deoxy-2′-fluoro-2′-methylcytidine derivatives of formula I wherein R1 is selected from C1-4-alkyl is described. The (2′R)-2′-deoxy-2′-fluoro-2′-methylcytidine derivatives of formula I have the potential to be useful as prodrugs for potent inhibitors of the Hepatitis C Virus (HCV) NS5B polymerase.