- Process for Preparation of Intermediates Used for the Synthesis of HIV Integrase Inhibitor
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Provided herein is a process for the intermediates used for preparation of HIV Integrase Inhibitor such as Bictegravir, Dolutegravir, Cabotegravir or their pharmaceutically acceptable salts.
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- CONTINUES FLOW PROCESS FOR THE PREPARATION OF ACTIVE PHARMACEUTICAL INGREDIENTS - POLYCYCLIC CARBAMOYL PYRIDONE DERIVATIVES AND INTERMEDIATES THEREOF
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The present invention discloses continues flow process for the preparation of polycyclic carbamoyl pyridone derivatives and intermediates thereof. In particular, the present invention discloses a process for the preparation of intermediate. Formule (V).
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- NOVEL POLYMOPRPHS AND SALTS OF POLYCYCLIC CARBAMOYL PYRIDONE DERIVATIVES
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The present invention provides novel polymorphs of (3S,11aR)-N-[(2,4-difluorophenyl) methyl]-6- hydroxy-3-methyl-5, 7-dioxo-2, 3,5,7, 11, 11a-hexahydro[1, 3]oxazolo[3, 2-a]pyrido[1, 2-d]pyrazine-8-carboxamide including sodium and potassium salts and pharm
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Page/Page column 39
(2018/07/05)
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- Intermediate of these pyridonecarboxylic carbamoylalkanoic and HIV integrase inhibitor
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A synthesis approach providing an early ring attachment via a bromination to compound I-I yielding compound II-II: whereby a final product such as AA: can be synthesized. In particular, the 2,4-difluorophenyl-containing sidechain is attached before creation of the additional ring Q.
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- An Efficient and Highly Diastereoselective Synthesis of GSK1265744, a Potent HIV Integrase Inhibitor
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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
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p. 564 - 567
(2015/03/04)
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- (3S,11aR)-6-[(phenylmethyl)oxy]-3-methyl-2,3,11,11a-tetrahydrooxazolo[3,2-a]pyrido[1,2-d]pyrazine-5,7-dione of the formula P-9 and/or (3S,11aR)-6-[(phenymethyl)oxy]-8-bromo-3-methyl-2,3,11,11a-tetrahydrooxazolo[3,2-a]pyrido[1,2-d]pyrazine-5,7-dione of the formula P-10
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The compounds are intermediates in the preparation of therapeutic agents useful in the treatment of viral infections, particularly HIV infection. The compounds are (3S,11aR)-6-[(phenylmethyl)oxy]-3-methyl-2,3,11,11a-tetrahydrooxazolo[3,2-a]pyrido[1,2-d]pyrazine-5,7-dione of the formula P-9 and/or (3S,11aR)-6-[(phenylmethyl)oxy]-8-bromo-3-methyl-2,3,11,11a-tetrahydrooxazolo[3,2-a]pyrido[1,2-d]pyrazine-5,7-dione of the formula P-10.
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- PROCESS FOR PREPARING POLYCYCLIC CARBAMOYL PYRIDONE DERIVATIVES AND INTERMEDIATES THEREOF
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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.
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Page/Page column 40
(2015/12/08)
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- Carbamoyl pyridone HIV-1 integrase inhibitors 3. A diastereomeric approach to chiral nonracemic tricyclic ring systems and the discovery of dolutegravir (S/GSK1349572) and (S/GSK1265744)
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We report herein the discovery of the human immunodeficiency virus type-1 (HIV-1) integrase inhibitors dolutegravir (S/GSK1349572) (3) and S/GSK1265744 (4). These drugs stem from a series of carbamoyl pyridone analogues designed using a two-metal chelation model of the integrase catalytic active site. Structure-activity studies evolved a tricyclic series of carbamoyl pyridines that demonstrated properties indicative of once-daily dosing and superior potency against resistant viral strains. An inherent hemiaminal ring fusion stereocenter within the tricyclic carbamoyl pyridone scaffold led to a critical substrate controlled diastereoselective synthetic strategy whereby chiral information from small readily available amino alcohols was employed to control relative and absolute stereochemistry of the final drug candidates. Modest to extremely high levels of stereochemical control were observed depending on ring size and position of the stereocenter. This approach resulted in the discovery of 3 and 4, which are currently in clinical development.
- Johns, Brian A.,Kawasuji, Takashi,Weatherhead, Jason G.,Taishi, Teruhiko,Temelkoff, David P.,Yoshida, Hiroshi,Akiyama, Toshiyuki,Taoda, Yoshiyuki,Murai, Hitoshi,Kiyama, Ryuichi,Fuji, Masahiro,Tanimoto, Norihiko,Jeffrey, Jerry,Foster, Scott A.,Yoshinaga, Tomokazu,Seki, Takahiro,Kobayashi, Masanori,Sato, Akihiko,Johnson, Matthew N.,Garvey, Edward P.,Fujiwara, Tamio
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p. 5901 - 5916
(2013/08/23)
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- PROCESS FOR PREPARING CARBAMOYLPYRIDONE DERIVATIVES AND INTERMEDIATES
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The present invention relates to the preparation of carbamoylpyridone derivatives and intermediates.
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Page/Page column 9-10
(2011/10/13)
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- PROCESSES AND INTERMEDIATES FOR CARBAMOYLPYRIDONE HIV INTEGRASE INHIBITORS
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Processes are provided which create an aldehyde methylene, or hydrated or hemiacetal methylene attached to a heteroatom of a 6 membered ring without going through an olefinic group and without the necessity of using an osmium reagent. In particular, a comopound of formula (I) can be produced from (II) and avoid the use of an allyl amine: (formulae I and II) where R, P 1 P3, R3 and Rx are as described herein.
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Page/Page column 26-27
(2010/07/02)
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- POLYCYCLIC CARBAMOYLPYRIDONE DERIVATIVE HAVING HIV INTEGRASE INHIBITORY ACTIVITY
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The present invention is to provide a novel compound (I), having the anti-virus activity, particularly the HIV integrase inhibitory activity, and a drug containing the same, particularly an anti-HIV drug, as well as a process and an intermediate thereof. Compound (I) wherein Z1 is NR4; R1 is hydrogen or lower alkyl; X is a single bond, a hetero atom group selected from O, S, SO, SO2 and NH, or lower alkylene or lower alkenylene in which the hetero atom group may intervene; R2 is optionally substituted aryl; R3 is hydrogen, a halogen, hydroxy, optionally substituted lower alkyl etc; and R4 and Z2 part taken together forms a ring, to form a polycyclic compound, including e.g., a tricyclic or tetracyclic compound.
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Page/Page column 142-143
(2010/11/24)
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