36 results about "Velpatasvir" patented technology

The invention provides a novel synthesis method of hepatitis drug velpatasvir.Two intermediate compounds including a compound 4 and a compound III are utilized to synthesize the velpatasvir, the structures of the two compounds are as shown in the following formulas, wherein PG radical is t-butyloxycarboryl (Boc), carboxybenzyl (Cbz), acetyl, benzoyl or (S)-2-methoxyl acyl carbonyl amino-3-methyl-butyryl group (Moc-L-Valyl).

The invention relates to a preparation method of a Velpatasvir (GS-5816) intermediate compound which serves as a hepatitis C resisting compound and is as shown in a formula 1, as well as preparation methods of a compound as shown in a formula 3 and a compound as shown in a formula 9. The compound as shown in the formula 3 and the compound as shown in the formula 9 are used for preparing a compound as shown in a formula 2 by nucleophilic substitution under the alkaline conditions; the compound as shown in the formula 2 is used for preparing the compound as shown in the formula 1 by a coupling reaction in the presence of a metal catalyst.

The invention relates to a novel method for synthesizing 9- bromine-3-(2-bromoacetyl)-10,11-dihydro-5H-dibenzo [c, g] chromene-8(9h)-ketone. Cheap and available raw materials are utilized; the obtained compound can be applied to synthesis of an anti-hepatitis c medicine velpatasvir; the reaction is shown in the specification.

The invention provides a synthesis method of velpatasvir. The method comprises the following steps that reaction is performed on a compound of a structure shown as a formula (II) and a compound of a structure shown as a formula (III) to obtain a compound of a structure shown as a formula (IV); then, the compound of the structure shown as the formula (IV) is converted into the compound shown as the formula (I); the compound of the structure shown as the formula (II) and the compound of the structure shown as the formula (III) are directly subjected to carbon-hydrogen activation coupling; the generation of feature impurities in the synthesis step can be effectively avoided; meanwhile, a final product can be purified through continuous salifying crystallization; the post treatment process is simplified to a great degree; in addition, the purity of the obtained velpatasvir is greater than 99.0 percent; the maximum individual impurities are less than 0.1 percent.

The invention discloses a preparation method of velpatasvir intermediate, namely [9-bromine-3-(2-bromoacetyl)-10,11-dihydro-5H-bibenzo(c,g) chromene-8(9h)-one]. The structure of the intermediate corresponds to a formula VI as shown in the description. The method comprises the steps of by taking a compound, namely 4-bromoacetophenone as raw materials, carrying out chloromethylation, condensation, cyclization and bromination, and finally obtaining the velpatasvir intermediate of the formula VI. According to the method, the starting raw materials are cheap and easily available, the reaction conditions are mild, the rout is short, the yield is high and the preparation method is more suitable for industrial production.

The invention relates to a synthesizing method of velpatasvir. The synthesizing method has the advantages that the novel raw materials and novel intermediates are adopted, the number of reaction stepsis reduced, the usage amount of onium salt is reduced, the defects of longer reaction route, lower total yield rate and unsuitability to industrial production amplification in the synthesizing methodof the prior art are overcome, and the production cost is effectively reduced.

The invention relates to a new velpatasvir intermediate crystal form. Specifically, the invention discloses a polymorphic substance of the formula I compound and a preparation method thereof. The polymorphic substance has good purifying effect.

The invention discloses a method for preparing an NS5A inhibitor-Velpatasvir, wherein the method mainly comprises the five steps: 1) carrying out docking reaction on reaction initial raw materials VPM1, VPM2 and VPM3 under the catalytic action of alkali to prepare an intermediate VP1; 2) removing amino protecting groups from the intermediate VP1 by using a protecting group removing reagent to prepare an intermediate VP2; 3) carrying out cyclization on the intermediate VP2 and an amine compound to prepare an intermediate VP3; 4) carrying out a reaction on the intermediate VP3 with VPM4 under the action of a condensing agent to prepare an amide compound intermediate VP4; and 5) carrying out oxidation reaction on the intermediate VP4 under the action of an oxidizing agent to prepare Velpatasvir. The preparation process of Velpatasvir has the characteristics of simplified route, simple reaction conditions, enhanced operability and higher product yield, and is more suitable for large-scaleindustrial production.

The embodiment of the invention discloses a synthesis method of a Velpatasvir intermediate A, and further provides three novel compounds for synthesis of the intermediate A: a compound I, a compound I1 and a compound I2. The method for the synthesis of the Velpatasvir intermediate A has the characteristics of low cost, environment friendliness and suitability for industrialized production.

The invention discloses a preparation method of an anti-hepatitis C medicine Velpatasvir intermediate 10,11-dihydro-5H-benzo[d]naphtha[2,3-b]pyranone derivative which is 9-bromo-3-(2-bromoacetyl)-10,11-dihydro-5H-benzo[d]naphtho[2,3-b]pyran-8(9H)-one (V). The preparation method concretely comprises the following steps: carrying out coupling cyclization on a raw material 7-((2-bromo-5-chlorophenyl)oxo)-3,4-dihydronaphthalen-1(2H)-one under the action of a ligand and an alkali to synthesize 3-chloro-10,11-dihydro-5H-benzo[d]naphtho[2,3-b]pyran-8(9H)-one, substituting chlorine by using sodium cyanide to form cyanide, prearing an organic acid from the cyanide under the action of an alkali, processing the organic acid by a lithium methide reagent to obtain 3-acetyl-10,11-dihydro-5H-benzo[d]naphtho[2,3-b] ]pyran-8(9H)-one, and carrying out a two-step bromination reaction to obtain the anti-hepatitis C medicine Velpatasvir intermediate. The method provides a brand new synthesis route of the anti-hepatitis C medicine Velpatasvir intermediate, and has the advantages of easily controlled reaction steps, and realization of stable industrial production preparation.

The invention relates to the technical field of medicine, in particular to a synthesis method of a velpatasvir intermediate A. Proper reactants are selected for synthesis of the velpatasvir intermediate A, a linear synthesis mode is changed into a convergence synthesis mode, and the method is mild in reaction condition, simple in step, high in synthesis efficiency, environmentally friendly and beneficial to industrial production and has good application prospects and market potentials. Besides, the invention also provides an intermediate compound for synthesizing the velpatasvir intermediate A.