Tag: M.W=400-500

Pace, Paola published the artcileDihydroxypyrimidine-4-carboxamides as Novel Potent and Selective HIV Integrase Inhibitors, Application In Synthesis of 519028-33-2, the main research area is pyrimidinecarboxamide dihydro preparation HIV integrase inhibitor.

Human immunodeficiency virus type-1 (HIV-1) integrase, one of the three constitutive viral enzymes required for replication, is a rational target for chemotherapeutic intervention in the treatment of AIDS that has also recently been confirmed in the clin. setting. We report here on the design and synthesis of N-benzyl-5,6-dihydroxypyrimidine-4-carboxamides as a class of agents which exhibits potent inhibition of the HIV-integrase-catalyzed strand transfer process. In the current study, structural modifications on these mols. were made in order to examine effects on HIV-integrase inhibitory potencies. One of the most interesting compounds for this series is 2-[1-(dimethylamino)-1-methylethyl]-N-(4-fluorobenzyl)-5,6-dihydroxypyrimidine-4-carboxamide, with a CIC95 of 78 nM in the cell-based assay in the presence of serum proteins. The compound has favorable pharmacokinetic properties in preclin. species (rats, dogs, and monkeys) and shows no liabilities in several counterscreening assays, highlighting its potential as a clin. useful antiviral agent.

Journal of Medicinal Chemistry published new progress about Homo sapiens. 519028-33-2 belongs to class pyrimidines, name is Benzyl (2-(4-((4-fluorobenzyl)carbamoyl)-5-hydroxy-6-oxo-1,6-dihydropyrimidin-2-yl)propan-2-yl)carbamate, and the molecular formula is C23H23FN4O5, Application In Synthesis of 519028-33-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Summa, Vincenzo published the artcile4,5-Dihydroxypyrimidine Carboxamides and N-Alkyl-5-hydroxypyrimidinone Carboxamides Are Potent, Selective HIV Integrase Inhibitors with Good Pharmacokinetic Profiles in Preclinical Species, Quality Control of 519028-33-2, the main research area is pyrimidinecarboxamide derivative preparation HIV integrase structure activity.

The dihydroxypyrimidine carboxamide 4a was discovered as a potent and selective HIV integrase strand transfer inhibitor. The optimization of physicochem. properties, pharmacokinetic profiles, and potency led to the identification of (I) in the dihydroxypyrimidine series and (II) in the N-methylpyrimidinone series having low nanomolar activity in the cellular HIV spread assay in the presence of 50% normal human serum and very good pharmacokinetics in preclin. species.

Journal of Medicinal Chemistry published new progress about AIDS (disease). 519028-33-2 belongs to class pyrimidines, name is Benzyl (2-(4-((4-fluorobenzyl)carbamoyl)-5-hydroxy-6-oxo-1,6-dihydropyrimidin-2-yl)propan-2-yl)carbamate, and the molecular formula is C23H23FN4O5, Quality Control of 519028-33-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Humphrey, Guy R. published the artcileDevelopment of a Second-Generation, Highly Efficient Manufacturing Route for the HIV Integrase Inhibitor Raltegravir Potassium, HPLC of Formula: 519028-33-2, the main research area is Raltegravir Potassium preparation scaleup methylation amidoxime rearrangement green chem.

A manufacturing route for the synthesis of Raltegravir Potassium was developed via thermal rearrangement of amidoxime DMAD adducts to construct the key, highly functionalized hydroxypyrimidinone core, 2-(1-benzyloxycarbonylamino-1-methylethyl)-5,6-dihydroxypyrimidine-4-carboxylic acid Me ester. Utilizing this route, Raltegravir Potassium was prepared in nine linear chem. steps with 22% overall yield. A second-generation synthesis was subsequently developed that solved the key chem., productivity, and environmental impact issues of the initial synthesis. Highlights of the new synthesis include a highly selective methylation, 3-4-fold higher productivity, and a 65% reduction of combined organic and aqueous waste produced. The efficient second-generation manufacturing route provides Raltegravir Potassium in 35% overall yield.

Organic Process Research & Development published new progress about Green chemistry. 519028-33-2 belongs to class pyrimidines, name is Benzyl (2-(4-((4-fluorobenzyl)carbamoyl)-5-hydroxy-6-oxo-1,6-dihydropyrimidin-2-yl)propan-2-yl)carbamate, and the molecular formula is C23H23FN4O5, HPLC of Formula: 519028-33-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Stathakis, Christos I. published the artcile(Chloromethyl)dimethylchlorosilane-KF: A Two-Step Solution to the Selectivity Problem in the Methylation of a Pyrimidone Intermediate en Route to Raltegravir, Application of Benzyl (2-(4-((4-fluorobenzyl)carbamoyl)-5-hydroxy-6-oxo-1,6-dihydropyrimidin-2-yl)propan-2-yl)carbamate, the main research area is chloromethyldimethylchlorosilane silylation potassium fluoride desilylation pyrimidone methylation raltegravir synthesis.

The present work describes a two-step process, namely, silylation with (chloromethyl)dimethylchlorosilane and desilylation, to address the selectivity problem in the N-methylation of a pyrimidone intermediate toward the synthesis of the raltegravir active pharmaceutical ingredient [treatment of I with HMDS/(ClCH2)SiMe2Cl, then 4-fluorobenzylamine followed by KF afforded II (75-80%)]. The said methodol. delivers the desired drug substance in which the O-methylated impurity content is below the detection limit by high-performance liquid chromatog. anal. Moreover, this two-step, one-pot procedure provides an apparent advantage in terms of environmental impact with respect to the optimum approach described in the literature, while it compares equally well in terms of cost and operational simplicity.

Organic Process Research & Development published new progress about Chemoselectivity (chemoselective methylation). 519028-33-2 belongs to class pyrimidines, name is Benzyl (2-(4-((4-fluorobenzyl)carbamoyl)-5-hydroxy-6-oxo-1,6-dihydropyrimidin-2-yl)propan-2-yl)carbamate, and the molecular formula is C23H23FN4O5, Application of Benzyl (2-(4-((4-fluorobenzyl)carbamoyl)-5-hydroxy-6-oxo-1,6-dihydropyrimidin-2-yl)propan-2-yl)carbamate.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Electric Literature of 799842-07-2 ,Some common heterocyclic compound, 799842-07-2, molecular formula is C16H19BrFN3O2S, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.

Example 1 Preparation of Compound I A 2 L four-necked flask charged with 61 g of di(p-tolyl) phosphinate (compound (VII), prepared by referring to Org. Lett. 2005, 7, 4277?4280) and 1 L of tetrahydrofuran solution was cooled down to -20 C., followed by adding dropwise 109 mL of butyllithium solution (2.5 M) at the same temperature. After the addition is completed, the mixture was stirred for 30 minutes. A solution comprising N-(5-(bromomethyl)-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl)-N-methyl methanesulfonamide (compound V) was then added dropwise while keeping the temperature at -20 C. After the addition is completed, the reaction was continued until the starting materials were completely consumed. The reaction was quenched with 1 L of water. The liquid was separated. The aqueous phase was extracted with 0.5 L of ethyl acetate. The organic phase was combined, and concentrated. The resultant solid was recrystallized in toluene to give compound I with a yield of 87%, and HPLC purity of >99%. (0045) 1H NMR (400 MHz, CDCl3) delta: 1.24 (6H, d, J=6.4 Hz), 2.38 (6H, s), 3.423.51 (7H, m), 3.87 (2H, d), 6.896.93 (2H, m), 7.107.16 (6H, m), 7.287.32 (4H, m).

In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles. 799842-07-2, N-[5-Bromomethyl-4-(4-fluorophenyl)-6-isopropylpyrimidine-2-yl]-N-methylmethane sulfonamide, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Asymchem Laboratories (Tianjin) Co., Ltd.; Asymchem Life Science (Tianjin) Co., Ltd.; Tianjin Asymchem Pharmaceutical Co., Ltd.; Asymchem Laboratories (Fuxin) Co., Ltd.; Jilin Asymchem Laboratories Co., Ltd.; HONG, Hao; GAGE, James; LI, Jiuyuan; SHEN, Litao; ZHANG, Lei; DONG, Changming; (12 pag.)US2017/22169; (2017); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Reference of 147118-40-9 ,Some common heterocyclic compound, 147118-40-9, molecular formula is C23H30FN3O6S, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.

Example 12(E)-7-[4-(4-Fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5- yl](3i?,55)-3,5-dihydroxyhept-6-enoic acid, hemi-calcium salt I; Tetrahydrofuran (35 ml) is added to weighed methyl ester II (6 g). 40percent solution of LiOH (10 ml) is added to the solution over 5 minutes, and the heterogenous mixture is stirred vigorously for 3 hours and then poured into a separatory funnel containing demineralized water (150 ml) and hexane (50 ml). After complete separation, ethyl acetate (40 ml) is poured into the aqueous phase and calcium acetate (2 g) is added. After 10 minutes of vigorous stirring, the phases are separated, and the aqueous phase is reextracted with ethyl acetate (20 ml). The ethyl acetate extract is washed with demineralized water (2 x 5 ml), dried, and evaporated, and the evaporation residue is dissolved in acetone and sprayed into the stream of an inert gas. 4.5 g (74 percent) of amorphous rosuvastatin is obtained. HPLC: 99.1 percent.

In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles. 147118-40-9, Rosuvastatin methyl ester, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; ZENTIVA, a.s.; WO2007/121; (2007); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Application of 799842-07-2, Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps,and cheap raw materials. 799842-07-2, name is N-[5-Bromomethyl-4-(4-fluorophenyl)-6-isopropylpyrimidine-2-yl]-N-methylmethane sulfonamide. A new synthetic method of this compound is introduced below.

General procedure: Aq 1 M NaOH (9 mL, 1.5 equiv) was added to a stirred MeOH (20mL) solution of the appropriate aromatic thiol (7.2 mmol, 1.2equiv). The solution was stirred at r.t. for 15 min and then the heterocyclicalkyl bromide 2 or 3 (6 mmol, 1 equiv) was added. When rosuvastatin moiety bromides 2 were used, THF (10 mL) was also added to the mixture to improve solubility. After 18 h, the solvent was evaporated, the residue was dissolved in CH2Cl2 (50 mL), and washed with H2O (100 mL). The aqueous phase was additionally extracted with CH2Cl2 (2 × 25 mL). The combined organic phases were dried (MgSO4) and the solvent was evaporated. The residuewas recrystallized and the isolated product was dried in vacuumovernight at 60 C below 50 mbar to give the pure sulfide heterocyclic precursor 4 or 5 in 75-97% yield.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,799842-07-2, N-[5-Bromomethyl-4-(4-fluorophenyl)-6-isopropylpyrimidine-2-yl]-N-methylmethane sulfonamide, and friends who are interested can also refer to it.

Reference:
Article; Fabris, Jan; ?asar, Zdenko; Smilovi?, Ivana Gazi?; ?rnugelj, Martin; Synthesis; vol. 46; 17; (2014); p. 2333 – 2346;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Adding a certain compound to certain chemical reactions, such as: 139756-22-2, 4-Ethoxy-3-(1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzene-1-sulfonyl chloride, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound, Formula: C17H19ClN4O4S, blongs to pyrimidines compound. Formula: C17H19ClN4O4S

Using the procedure described in Example 1, the reaction solvent and proton scavenger were varied.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,139756-22-2, 4-Ethoxy-3-(1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzene-1-sulfonyl chloride, and friends who are interested can also refer to it.

Reference:
Patent; TEVA PHARMACEUTICAL INDUSTRIES LTD.; TEVA PHARMACEUTICALS USA, INC.; WO2005/67936; (2005); A2;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Electric Literature of 1421372-67-9, 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 1421372-67-9, name is N1-(2-(Dimethylamino)ethyl)-5-methoxy-N1-methyl-N4-(4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-2-nitrobenzene-1,4-diamine. This compound has unique chemical properties. The synthetic route is as follows.

1) Weigh 200g of the raw material hydrogenation precursor nitro compound, and then add it to a mixture of 4L of methanol and 100g of concentrated hydrochloric acid, stir and dissolve, then add 10g of Pd/C catalyst with Pd content of 10%, stir well and mix to form Material I, the material I is sent to the preheating module 1 of the microchannel reactor for preheating, and after preheating, enters the reaction module group of the microchannel reactor.2) The reaction module group that delivers hydrogen to the microchannel reactor and the step 1) the preheated material I reacts in the reaction module group, wherein: the flow rate of the slurry pump is adjusted so that the flow rate of the material I is 40.0 g/min. The flow rate of the H2 gas flow meter is adjusted to 500 ml/min, the molar ratio of the raw material hydrogenation precursor nitro compound to hydrogen is 1:3.5, the reaction temperature is 90 C, the temperature of the cooling module is 20 C, and the residence time of the reaction is 25s, the reaction pressure is 1.5Mpa, and the collection flows out from the outlet of the cooling module.The reaction solution is subjected to post-treatment, which means that the catalyst is recovered by filtration, and the solvent is distilled off under reduced pressure. The residue is added to 1 L of water, stirred and dissolved, and the pH of the system is adjusted to 9.0 by a NaOH solution having a mass fraction of 20%. 10.0, then join500ml of ethyl acetate was extracted and separated, the organic phase was discarded, the aqueous phase was stirred and crystallized at 10 C for 1 hour, filtered, and the product was washed with a small amount of ethanol, and vacuum dried at 50 C for 8 hours to obtain an oxetinib intermediate. Target product 160.65g, yield85.73%, purity 99.68%.

According to the analysis of related databases, 1421372-67-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Heilongjiang Xinchuang Bio-technology Development Co., Ltd.; Ren Jiqiu; Yang Kun; Li Haitao; (12 pag.)CN108484579; (2018); A;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Related Products of 1421372-67-9, With the rapid development and complex challenges of chemical substances, the synthesis of new drugs is usually one of the most effective ways to increase yield.1421372-67-9, name is N1-(2-(Dimethylamino)ethyl)-5-methoxy-N1-methyl-N4-(4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-2-nitrobenzene-1,4-diamine, molecular formula is C25H29N7O3, molecular weight is 475.5429, as common compound, the synthetic route is as follows.

A solution of N1- (2- (dimethylamino) ethyl) -5-methoxy-N1-methyl-N4- (4- (1-methylindol-3-yl) 2-nitrophenyl-1,4-diamine (30.0 g, 0.063 mol) was added to a 1 L vial,Adding 600 mL of tetrahydrofuran and 10 g of Raney nickel,Hydrogen gas at a pressure of 3 atm was introduced at room temperature,Reaction for 12 h.After the reaction is complete,The reaction solution was filtered through celite,To obtain a brown solution,Concentrated under reduced pressure to give crude brown solid,The crude product was purified by recrystallization from 250 mL of a mixture of ethyl acetate and n-heptane (1: 1 by volume of ethyl acetate and n-heptane in the mixture)To give a light brown solid N1- (2- (dimethylamino) ethyl) -5-methoxy -N1- methyl -N4- (4- (1- methyl-indol-3-yl) pyrimidine-2 – yl) phenyl-1,2,4-triamine 21.9g, yield 78%.

Statistics shows that 1421372-67-9 is playing an increasingly important role. we look forward to future research findings about N1-(2-(Dimethylamino)ethyl)-5-methoxy-N1-methyl-N4-(4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-2-nitrobenzene-1,4-diamine.

Reference:
Patent; Shanghai University of Engineering Science; Zhu, Guoqing; Mao, Yongjun; Zhu, Chunping; Wang, Han; (16 pag.)CN106366072; (2017); A;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia