Category: 274693-26-4

A catalyst don’t appear in the overall stoichiometry of the reaction it catalyzes, Formula: C26H32F2N6O4S, but it must appear in at least one of the elementary reactions in the mechanism for the catalyzed reaction. 274693-26-4, Name is 2-(((3aR,4S,6R,6aS)-6-(7-(((1R,2S)-2-(3,4-Difluorophenyl)cyclopropyl)amino)-5-(propylthio)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)oxy)ethanol, molecular formula is C26H32F2N6O4S. In an article, author is Maligres, Peter E.,once mentioned of 274693-26-4.

Synthesis of Fused Oxepane HIV Integrase Inhibitor MK-1376

Controlling the absolute and relative stereochemistry of a seven-membered oxepane in the formation of HIV integrase inhibitor MK-1376 was accomplished through a strategy involving the use of asymmetric allylation and stereoconvergent, substrate-directed installation of an amine fragment. Surprising reactivity was demonstrated during the asymmetric allylation in which the allyl-pyrimidone product was formed reversibly. The stereoconvergent amine addition was accomplished through an elimination/addition sequence involving a quinone methide reactive intermediate, and nucleophilic trapping of the reactive quinone methide intermediate with methylamine. This novel approach delivered MK-1376, offering 100-fold greater productivity and 50-fold less waste than the initial synthetic chemistry route.

If you¡¯re interested in learning more about 274693-26-4. The above is the message from the blog manager. Formula: C26H32F2N6O4S.

Reference:
Pyrimidine | C4H4N2 – PubChem,
,Pyrimidine – Wikipedia

Application of 274693-26-4, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 274693-26-4, name is 2-(((3aR,4S,6R,6aS)-6-(7-(((1R,2S)-2-(3,4-Difluorophenyl)cyclopropyl)amino)-5-(propylthio)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)oxy)ethanol, molecular formula is C26H32F2N6O4S, The compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

3) Operation process(1) cooling the toluene solution of the upper step product remaining in the 200L reaction vessel to 10 to 20 C;(2) adding 37.062 kg of hydrochloric acid and 55 L of methanol mixed solution cooled to 10 to 20 C into the reaction kettle under stirring;After the addition is completed, the mixture is kept at 10 to 20 C for 3 to 4 hours;(3) TLC detection reaction was completed, ethyl acetate: isooctane=1:1, taking the upper organic phase point plate;Stop stirring, let stand for stratification, and separate the lower methanol water phase for use;(4) Add 500 ml of the lower methanol aqueous phase separated in the above step, and add 20% potassium carbonate aqueous solution with stirring.(25.406 kg of potassium carbonate and 101.64 L of purified water); finally adjusted pH between 7-9;(5) adding 55 L of ethyl acetate under stirring, and stirring for 30 min;Stop stirring, let stand layering, separate the lower layer of water, and transfer the upper organic phase to the PE barrel for use;(6) The lower aqueous phase was transferred to the reaction vessel, 55 L of ethyl acetate was added, and the mixture was stirred for 30 min; the stirring was stopped, and the layer was allowed to stand.Divide the lower aqueous phase;(7) Combine the two organic phases, add 200L reaction kettle, add 55L purified water with stirring, stir for 30 minutes; stopStirring, standing layering, separating the lower aqueous phase; adding 55 L of purified water to the reactor, stirring for 30 minutes; stopping stirring, quenchingLayering, separating the lower aqueous phase;(8) Add 686 g of activated carbon to the organic phase (the amount of activated carbon is 5% of the crude product, and the crude product is 100% yield)Calculated), heated to 40 ~ 50 C, stirred for 30 minutes;(9) Filter the filter pad with diatomaceous earth (about 100g of diatomaceous earth), distill off the solvent under reduced pressure at 50 C, steam until no more liquidThe body is effluent; add 11 L of ethyl acetate to distill off the solvent, repeat 2 times until the solid is produced, no more liquid will flow out;Add 68.61 L of ethyl acetate and heat to 50-60 C to dissolve (the amount of ethyl acetate is 5 times the mass of the crude product, the crude product is100% yield calculation); transfer the solution into a 50L reaction kettle, heated to 50 ~ 60 C;(10) Add 82.33L of isooctane preheated to 50-60 C under stirring (the amount of isooctane is ethyl acetate volume)1.2 times); control the addition speed to keep the internal temperature above 50 C, and gradually precipitate solids during the addition;(11) After the addition is completed, the temperature is lowered by stirring to a temperature of 20 to 30 C, and stirred for 1 hour;(12) further cooling to 0 to 10 C and stirring for 2 hours;(13) Centrifugal filtration, the reaction kettle and the filter cake were pretreated to 13.72 L of ethyl acetate and 16.47 L of isothermally cooled to 0 to 10 C.Washed with octane mixed solvent;(14) The filter cake is dried under vacuum at 45-55 C for 8 to 12 hours to obtain 11.6 kg of crude tigrilo (Im-4);85; 1) Add 45 L of dichloromethane and 108 L of tert-butanol to a 200 L crystallizer; stir and add 11.5 kg of ticagrelor.Product,(2) heating to 50 ~ 60 C under stirring for 1 hour; cooling to 20 ~ 30 C, stirring for 1 hour;(3) further cooling to 0 to 10 C for 2 hours;(5) centrifugal filtration, the reaction kettle and the filter cake are rinsed with water precooled to 0 to 10 C;(6) The filter cake was dried under vacuum at 45-55 C for 8 to 12 hours to obtain 10.7 kg of ticagrelor; the weight yield was 93%.

According to the analysis of related databases, 274693-26-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Hebei Kaiwei Pharmaceutical Co., Ltd.; Pang Yuning; (23 pag.)CN108276417; (2018); A;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Application of 274693-26-4, In the chemical reaction process,reaction time,type of solvent,can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product.An updated downstream synthesis route of 274693-26-4 as follows.

(1) The toluene solution of the previous product left in the 100L glass reactor was cooled to 20 C;(2) stirring was cooled to 20 C 21.409kg of hydrochloric acid and 30.75L of methanol was added to the reaction mixture of the reaction vessel; addition was completed and maintained at 20 C for 4h;(3) TLC (ethyl acetate: isooctane = 1: 1, take the upper organic point plate), FTG-3 raw material point disappears, the reaction is complete; stop stirring,Static stratification, separation of the lower methanol aqueous standby;(4) 500L reactor was added to the lower part of the lower methanol aqueous phase,With stirring, 20% aqueous potassium carbonate was added(14.202 kg of potassium carbonate and 56.81 L of purified water);Finally adjust the pH between 9;(5) adding 30.75L of ethyl acetate with stirring, stirring for 30min;Stop stirring, standing stratification, separation of the lower aqueous phase,The upper organic phase into the PE barrel backup;(6) into the lower aqueous phase reactor, 30.75L of ethyl acetate was added,Stirring 30min; stop stirring, standing stratification, separation of the lower aqueous phase;(7) The two organic phases were combined, added to a 100L glass reactor,30.75L purified water was added with stirring, stirred for 30min; stop stirring, standing stratification, separation of the lower aqueous phase;30.75L of purified water was added to the reaction kettle and stirred for 30 minutes;Stop stirring, stratification, leaving the lower aqueous phase;(8) To the organic phase, 384 g of activated carbon (5% of the amount of active carbon is used as crude product and the crude product is calculated in 100% yield) is heated to 50 C,Stir for 30min;(9) was filtered, the filtrate was evaporated under reduced pressure at 50 C solvent,Steamed until there is no liquid outflow; then add ethyl acetate 6.15L steamIn addition to the solvent, repeat 2 times, until the solid is generated, there is no liquid outflow;(10) To the residue was added 38.40L of ethyl acetate was heated to 60 C dissolved (ethyl acetate was used in an amount of 5 times the volume of the crude product, the crude product in 100% yield); The solution was transferred to a 100L glass reactor, heated To 60 C;(11) 46.08 L isooctane (isooctane in an amount of 1.2 times the volume of ethyl acetate) preheated to 60 C was added with stirring; the addition rate was controlled,Keep the internal temperature above 50 C ,During the process of solid precipitation gradually;(12) is added, cooled to 30 C with stirring, stirred for 1h;(13) and then cooled to 10 C and stirred for 2h;(14) was filtered, the reactor and the filter cake with precooled to 0 ~ 10 C of 7.68L ethyl acetate and 9.22L isooctane mixed solvent leaching;(15) The filter cake was dried under reduced pressure at 60 C for 12h to obtain crude product of ticagrelor, with white or almost white crystalline powder 6.577kg; yield 87%.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,274693-26-4, its application will become more common.

Reference:
Patent; Hunan Tianji Caotang Pharmaceutical Co., Ltd.; Song Taifa; Li Linmei; Xiang Zhongyou; Weng Xiaotao; Xia Zhike; He Yanbo; Suo Chenglin; Peng Fangwei; (13 pag.)CN107337675; (2017); A;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Electric Literature of 274693-26-4, The major producers of chemicals have been the Europe, Japan and China. Due to the growing call for a cleaner, greener environment, people will have to find innovative ways to maintain their relevance. Here is a compound 274693-26-4, name is 2-(((3aR,4S,6R,6aS)-6-(7-(((1R,2S)-2-(3,4-Difluorophenyl)cyclopropyl)amino)-5-(propylthio)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)oxy)ethanol. This compound has unique chemical properties. The synthetic route is as follows.

To a reaction mixture of 7.7 g (0.01368 moles) 2-[[(3aR,4S,6R,6aS)-6-[7-[[(1 R,2S)-2-(3,4- difluorophenyl)cyclopropyl]amino]-5-(propylthio)-3H-1 ,2,3-triazolo[4,5-d]pyrimidin-3-yl]-2,2- dimethyltetrahydro-3aH-cyclopenta[d][1 ,3]dioxol-4-yl]oxy]-1-ethanol of formula VII in 15 ml methanol, 15 ml concentrated hydrochloric acid was charged and the reaction mixture was stirred at room temperature for 2-3 hours. The reaction mixture was cooled to 0C to 5C and neutralized with 30 ml aqueous ammonia and extracted two times with 25 ml ethyl acetate, ethyl acetate layers were combined and washed with 25 ml water. Ethyl acetate layer was distilled under reduced pressure at 40C. Ticagrelor was isolated from 20% acetone in heptane mixture and dried under vacuum at 45C to 50C. Yield = 5.36g (Efficiency – 75%, HPLC -99.4%).

While traditionally a conservative industry, chemical producers will need to modernize their PR strategies to stay relevant.we look forward to future research findings about 274693-26-4, 2-(((3aR,4S,6R,6aS)-6-(7-(((1R,2S)-2-(3,4-Difluorophenyl)cyclopropyl)amino)-5-(propylthio)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)oxy)ethanol.

Reference:
Patent; CIPLA LIMITED; COTTRILL, Emily; RAO, Dharmaraj Ramachandra; MALHOTRA, Geena; PHULL, Manjinder Singh; GHAGARE, Maruti; (34 pag.)WO2016/30704; (2016); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia