166376-97-2

Usage

InChI:InChI=1/C10H16F2O5/c1-4-15-8(14)10(11,12)7(13)6-5-16-9(2,3)17-6/h6-7,13H,4-5H2,1-3H3/t6-,7-/m0/s1

Upstream product

• 667-27-6 Ethyl bromodifluoroacetate 
• 15186-48-8 2,3-isopropylidene-glyceraldehyde 
• 1707-77-3 1,2:5,6-di-O-isopropylidene-D-mannitol 
• 50271-42-6 5,6-O-isopropylidene-D-isoascorbic acid 
• 136136-17-9 O³,O⁴-(1-methylethylidene)-D-erythronic acid 
• 22323-80-4 (4S)-2,2-dimethyl-[1,3]dioxolane-4-carbaldehyde 
• 942296-13-1 ethyl (D-erythro)-3-(4-chlorophenylcarbamoyloxy)-2,2-difluoro-3-(2,2-dimethyl-dioxalane-4-yl)propionate 
• 928797-50-6 ethyl (3R,S)-2,2-difluoro-3-hydroxy-(2,2-dimethyldioxolpent-4-yl)propionate 
• 53735-98-1 (1S,2S)-1,2-bis[(R)-2,2-dimethyl-1,3-dioxolan-4-yl]ethane-1,2-diol 
• 383-62-0 ethyl 2-chloro-2,2-difluoroacetate 
• 109522-62-5 (2-ethoxy-1,1-difluoro-2-oxoethyl)zinc(II) bromide 
• 15042-01-0 5,6-O-isopropylidene-L-ascorbic acid 
• 92973-39-2 O³,O⁴-(1-methylethylidene)-L-threonic acid 
• 5736-03-8 (d,l) isopropylidene glyceraldehyde 

Downstream Products

• 95058-92-7 (erytro) ethyl-3-(2,2-dimethyl-1,3-dioxolan-4-yl)-2,2-difluoro-3-hydroxy propionate 
• 122111-01-7 2-deoxy-2,2-difluoro-D-erythro-pentonic acid γ-lactone 3,5-dibenzoate 
• 1173824-58-2 (2R,3R)-2-((benzoyloxy)methyl)-4,4-difluoro-5-hydroxyoxolan-3-yl benzoate 
• 134877-42-2 3,5-di-O-benzoyl-2-deoxy-2,2-difluoro-1-O-methanesulfonyl-D-erythro-pentofuranose 
• 95058-77-8 2-deoxy-2,2-difluoro-1-carbonylribose 
• 1147119-08-1 C₇H₁₂F₂O₅ 
• 1147119-10-5 (3R,4R)-2,2-Difluoro-3,4,5-trihydroxy-pentanoic acid 
• 122111-03-9 gemcitabine hydrochloride 
• 166275-25-8 (4S,5S)-3,3-Difluoro-4-hydroxy-5-hydroxymethyl-dihydro-furan-2-one 
• 166275-26-9 (4S,5S)-4-(tert-Butyl-dimethyl-silanyloxy)-5-(tert-butyl-dimethyl-silanyloxymethyl)-3,3-difluoro-dihydro-furan-2-one 
• 211807-33-9 (R)-3,3-Difluoro-5-hydroxymethyl-dihydro-furan-2-one 

Relevant academic research and scientific papers

Deoxyribonolactone lesion in DNA: Synthesis of fluorinated analogues

Mono- and difluorinated derivatives of 2-deoxyribonolactone were synthesized using diastereoselective Reformatski reaction as a key step.

High-selectivity synthesis method for gemcitabine intermediate

The invention discloses a high-selectivity synthesis method for a gemcitabine intermediate. The high-selectivity synthesis method specifically comprises the following process: Step 1, synthesis of T1;Step2, synthesis of T2, to be specific, 550kg of hydrogen peroxide is dropwise added into the T1, and a reaction is controlled to produce the T2; Step3, synthesis of T3, to be specific, sodium acetate trihydrate or sodium carbonate is added into a reaction kettle, the PH value is adjusted with glacial acetic acid, a 10%-15% sodium hypochlorite aqueous solution is dropwise added, and a reaction iscontrolled to produce the T3; Step 4, synthesis of T4; Step 5, synthesis of T5; Step 6, synthesis of T6; Step 7, synthesis of T7; Step 8, synthesis of T8; and Step9, T8 configuration transformation.The high-selectivity synthetic method for the gemcitabine intermediate can reduce the production cost, and meanwhile, can also increase the yield of the gemcitabine intermediate.

Preparation method of gemcitabine key intermediate

The invention relates to a preparation method of a gemcitabine key intermediate, and belongs to the technical field of drug intermediate synthesis. In order to solve the problems of high reaction condition requirements and high raw material cost in the prior art, the invention provides a preparation method of a gemcitabine key intermediate, which is characterized by comprising the following steps of: adding ethyl difluorochloroacetate, magnesium metal and a silanization reagent into a polar organic solvent for reaction to obtain an intermediate silyl enol ether; and under the action of Lewis acid, carrying out an aldol condensation reaction on the silyl enol ether and a compound R-glyceraldehyde acetonide as shown in a formula Vto obtain a corresponding product, namely, a gemcitabine key intermediate. According to the method, a target product with high chiral purity and yield can be effectively generated, the product yield reaches 85% or above, and the chiral purity of the product reaches 95% or above.

Preparation method of antitumor drug gemcitabine hydrochloride

The invention discloses a preparation method of an antitumor drug gemcitabine hydrochloride. The preparation method specifically comprises the following processes: (1) preparing an antitumor drug gemcitabine hydrochloride intermediate: Step 1, synthesis of T1; Step2, synthesis of T2; Step3, synthesis of T3; Step4, synthesis of T4; Step5, synthesis of T5; and Step6, synthesis of T6; and (2) preparing gemcitabine hydrochloride from the gemcitabine hydrochloride intermediate: Step7, firstly reducing T6 with lithium tri (tert-butoxy) aluminum hydride, and then acylating with paratoluensulfonyl chloride to prepare T7, wherein T7 is 2-deoxy-2, 2-difluoro-D-ribofuranose-3, 5-dibenzoate; and Step8, reacting T7 with cytosine under the action of a catalyst to generate T8, wherein T8 is 2'-deoxy-2',2'-difluorocytidine-D-ribofuranose-3',5'-dibenzoate. The preparation method of the antitumor drug gemcitabine hydrochloride has the advantages of low production cost, favorability for industrial production and small environmental pollution.

Preparation method of intermediate of antitumor drug gemcitabine hydrochloride

The invention relates to a preparation method of a intermediate of antitumor drug gemcitabine hydrochloride. According to the method, D-isoascorbic acid is used as a starting raw material and reacts with 2,2-dimethylpropane under the catalysis of p-toluenesulfonic acid in the presence of acetone serving as a solvent to protect hydroxyl groups at 5 and 6 sites to obtain T1; then, hydrogen peroxideis used for carrying out oxidation under the alkaline condition to obtain T2; the T2 is oxidized by sodium hypochlorite to obtain T3; the T3 and ethyl bromodifluoroacetate are subjected to a Reformatsky reaction to obtain T4; then the T4 is subjected to deprotection and cyclization under the catalysis of trifluoroacetic acid to obtain T5; the T5 and benzoyl chloride are subjected to an esterification reaction under the catalysis of DMAP to obtain T6, and a synthetic route II is shown in the specification.

Method for preparing Gemcitabine intermediate from chiral catalyst

The invention relates to a method for preparing a Gemcitabine intermediate from a chiral catalyst, and belongs to the technical field of synthesis of medical intermediates. In order to solve the problem that the existing reaction is poor in stereoselectivity, the invention provides the method for preparing the Gemcitabine intermediate from the chiral catalyst; the method comprises the following steps: performing a condensation reaction on R-glyceraldehyde acetonide and difluoro halogenated ethyl acetate in an inert organic solvent under the combined catalytic action of active zinc powder and delta-amino alcohol ligands to obtain a corresponding intermediate; performing deprotection and lactonization treatment on the intermediate and performing a reaction on the intermediate and benzoyl chloride in the presence of an acid-binding agent to obtain the corresponding Gemcitabine intermediate. A product obtained with the method provided by the invention has an ee value being as high as 98% or above, the content of an erythro form product is high, and the obtained product does not need to be refined and can be directly used for next reaction.

Preparation method of gemcitabine intermediate

The invention relates to a preparing method of a gemcitabine intermediate, and belongs to the technical field of medicine intermediate synthesis. In order to solve the problems that an existing methodis violent in reaction and not stable in yield, the preparing method of the gemcitabine intermediate is provided. The method includes the steps of adding iodine powder to an organic zinc intermediate-state reaction solution obtained through the reaction of ethyl bromodifluoroacetate and activated zinc powder in a first solvent, adding acetonylidene glyceraldehyde to a second solvent to obtain a corresponding acetonylidene glyceraldehyde solution, synchronous pumping the organic zinc intermediate-state reaction solution and the acetonylidene glyceraldehyde solution into a micro-channel reactorfor a condensation reaction to obtain outflow liquid, and conducting acidification to obtain the corresponding product (gemcitabine intermediate). The problem of the violent reaction can be effectively overcome, and the effects of mild reaction and high product yield are achieved.

Novel preparation method for gemcitabine hydrochloride

The invention discloses a preparation method for gemcitabine hydrochloride. The preparation method comprises the steps: carrying out condensation, cracking and addition on D-mannitol serving as an initial raw material, and protecting hydroxyl by TESC1 to prepare an intermediate; and after carrying out condensation on the intermediate and cytosine under the catalysis of chiral phosphoric acid, carrying out salification to prepare gemcitabine hydrochloride. The preparation method has the advantages that the reaction steps are reduced, and the cost is reduced. Due to the use of the chiral phosphoric acid, the proportion of a required beta structure is greatly increased, the ratio of beta to alpha can reach 9:1, and the yield is increased. The chiral phosphoric acid belongs to an organic acidand is recyclable, little to environment pollution and particularly suitable for industrial production of gemcitabine hydrochloride.

1,3-dimethyl-7-substituted quinazoline-2,4-dione fluorine-containing amide compound and synthesizing method and application thereof

The invention discloses a 1,3-dimethyl-7-substituted quinazoline-2,4-dione fluorine-containing amide compound. The 1,3-dimethyl-7-substituted quinazoline-2,4-dione fluorine-containing amide compound is shown as a general formula in the specification, wherein R1 refers to hydrogen or ethyl, and R2 refers to a benzene ring, a benzene ring derivative, a heterocyclic ring or fatty hydrocarbon. Biological activity test experiments prove that the 1,3-dimethyl-7-substituted quinazoline-2,4-dione fluorine-containing amide compound shows good inhibiting activity for Monilia albicans, Cryptococcus neoformans and Aspergillus fumigates, is remarkable in chitin synthetase inhibiting activity and good in antibacterial effect and can be used for preparing drugs for resisting pathogenic microorganisms.

STEREOSELECTIVE SYNTHESIS OF BETA-NUCLEOSIDES

A process of stereoselectively synthesizing β-nucleoside of formula (I), e.g., 2'-deoxy-2,2'-difluorocytidine, is described. The process includes reacting a tetrahydrofuran compound of the following formula: in which wherein R1, R2, R3, R4, and L as defined in the specification, with a nucleobase derivative in the presence of an oxidizing agent.