- Preparation method of multi-tenefavirin open-loop impurities and impurities thereof (by machine translation)
-
Compared with the prior art, the method disclosed by the invention disclosed by the, invention is A simple in B reaction conditions, and the 1 reaction operation safety, of the 2 impurities of the 3, impurities of the impurities of the 4, impurities and the 5 impurities of the 6, A impurities 6 and the impurities of the impurities and the impurities of the A, impurities B; A B ; A B, A B, B. (by machine translation)
- -
-
Paragraph 0071-0075
(2020/01/25)
-
- Synthesis method of diastereoisomer impurities in dolutegravir raw materials and intermediates
-
The invention provides a synthesis method of diastereoisomer impurities in dolutegravir raw materials and intermediates. The synthesis method comprises the following steps: 1) with a compound V as a starting raw material, performing a reaction with a large-steric-hindrance protecting group under an alkaline condition to generate a compound VII; 2) carrying out alcoholysis on the compound VII and areaction solvent under an alkaline condition to generate a compound VIII; and 3) carrying out hydrolysis on the compound VIII and an alcohol solvent under an alkaline condition to obtain a compound IX. The invention provides the synthesis method of the diastereoisomer impurities in dolutegravir raw materials and intermediates, which is simple in process and easily available in raw materials. Theprepared new impurity can provide a reference substance for quality analysis of dolutegravir, so that the quality standard of dolutegravir is improved.
- -
-
Paragraph 0027; 0050-0052
(2019/10/01)
-
- Method for synthesizing diastereomer impurity in dolutegravir raw material
-
The invention provides a method for synthesizing a diastereomer impurity in a dolutegravir raw material, which comprises the following steps: 1, carrying out condensation reaction on SM1 serving as araw material and 2,4-difluorobenzylamine to generate a compound I; 2, reacting the compound I with an alkali in a reaction solvent to generate a compound II; 3, hydrolyzing the compound II under an acidic condition to generate a compound III; 4, carrying out acid catalytic reaction on the compound III and R-aminobutanol in a reaction solvent to generate a compound IV; 5, generating a compound V from the compound IV in a reaction solvent under the catalysis of a condensing agent; and 6, demethylating the compound V under the action of an alkali metal salt to generate an impurity VI. The synthetic method of the diastereoisomer impurity in the dolutegravir raw material is simple in process and available in raw material, and the prepared new impurity can provide a reference substance for quality analysis of dolutegravir, so that the quality standard of dolutegravir is improved.
- -
-
Paragraph 0027-0030; 0031
(2019/11/13)
-
- 7-Step Flow Synthesis of the HIV Integrase Inhibitor Dolutegravir
-
Dolutegravir (DTG), an important active pharmaceutical ingredient (API) used in combination therapy for the treatment of HIV, has been synthesized in continuous flow. By adapting the reported GlaxoSmithKline process chemistry batch route for Cabotegravir, DTG was produced in 4.5 h in sequential flow operations from commercially available materials. Key features of the synthesis include rapid manufacturing time for pyridone formation, one-step direct amidation of a functionalized pyridone, and telescoping of multiple steps to avoid isolation of intermediates and enable for greater throughput.
- Ziegler, Robert E.,Desai, Bimbisar K.,Jee, Jo-Ann,Gupton, B. Frank,Roper, Thomas D.,Jamison, Timothy F.
-
supporting information
p. 7181 - 7185
(2018/06/15)
-
- A new method for preparing lu Tewei (by machine translation)
-
A process for preparing lu Tewei (E) new method, relates to the field of pharmaceutical chemistry, comprising the following steps: step 1) by the compound (A) with 2, 4 - two fluorine animal pen amine condensation reaction to obtain compound (B) steps 2) compound (B) removing the aldehyde protecting group to obtain the compound (C) step 3) compound (C) with R - 3 - amino - 1 - butanol on the ring by the reaction of the compound (D) step 4) compound (D) by the methylation reaction to occur after lu Tewei (E). This invention adopts the new line, and to the continuous optimization of the reaction conditions, so that the overall yield is raised greatly, as the compound (A) as a starting material and calculate the total yield is 75% or more, in a single reaction yield is 90% or more. (by machine translation)
- -
-
Paragraph 0029-0031; 0038-0040
(2017/08/28)
-
- NOVEL PROCESS FOR THE PREPARATION OF DOLUTEGRAVIR AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
-
The present invention relates to a novel process for the preparation of dolutegravir and pharmaceutically acceptable salts thereof using novel intermediates.
- -
-
Paragraph 00261-00262
(2015/12/17)
-
- PROCESS FOR PREPARING POLYCYCLIC CARBAMOYL PYRIDONE DERIVATIVES AND INTERMEDIATES THEREOF
-
The present invention relates to a novel process for the synthesis of polycyclic carbamoyl pyridone derivativesof formula (B): wherein Ar, W1, W2, W3, X, Y and Z are as defined in the specification; and to novel chemical intermediates for use in sucha process.
- -
-
Page/Page column 45-46
(2015/12/08)
-
- An Efficient and Highly Diastereoselective Synthesis of GSK1265744, a Potent HIV Integrase Inhibitor
-
A novel synthesis of GSK1265744, a potent HIV integrase inhibitor, is described. The synthesis is highlighted by an efficient construction of the densely functionalized pyridinone core as well as a highly diastereoselective formation of the acyl oxazolidine moiety. The latter exploits the target molecules ability to chelate to Mg2+, a key feature in the integrase inhibitors mechanism of action.
- Wang, Huan,Kowalski, Matthew D.,Lakdawala, Ami S.,Vogt, Frederick G.,Wu, Lianming
-
supporting information
p. 564 - 567
(2015/03/04)
-
- POLYCYCLIC-CARBAMOYLPYRIDONE COMPOUNDS AND THEIR PHARMACEUTICAL USE
-
Compounds for use in the treatment of human immunodeficiency virus (HIV) infection are disclosed. The compounds have the following Formula (I): including stereoisomers and pharmaceutically acceptable salts thereof, wherein R1, X, W, Y1, Y2, Ζ1 and Z4 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.
- -
-
Page/Page column 43-44
(2014/07/08)
-