Day: October 12, 2022

Gruessner, A.; Montavon, M.; Schnider, O. published the artcile< Disubstituted 4-sulfanilamidopyrimidines>, Formula: C5H4Cl2N2O, the main research area is .

A series of 5,6-dialkoxy-4-sulfanilamidopyrimidines was prepared and tested for chemotherapeutic activity. Thus, to a mixture of 1 mole ROCH2CO2Me, 1200 ml. benzene, and 1.5 moles oxalic acid dialkyl ester was added in small portions at 22° during 3 hrs. with cooling and stirring 60 g. NaOMe. The mixture was stirred overnight, worked up, the crude product heated with 3 g. glass powder and 5 mg. Fe powder at 210°/400 mm. for 3 hrs. followed by distillation at 11 mm. After distillation was complete the residue was heated with an addnl. 5 g. glass powder and 5 mg. iron powder for 3 hrs. at 210° and then distilled at 11 mm. The successive distillations gave ROCH(CO2Me)2 (I). I was converted to the diamide ROCH(CONH2)2 (II) by treatment with liquid NH3 for 14 hrs. at room temperature The table lists the methyl esters and amides prepared I, II; R, b11, % yield, M.p. (H2O), % yield; Me, 103-4°, 78, 217-18°, 97; Et, 114-16°, 80, 202°, 97; iso-Pr, 118-21°, 72, 218-19°, 94; Pr, 124-8°, 65, –, –; Bu, 128-30°, 63, 174-6°, 85; To a solution of 20.4 g. Na in 410 ml. absolute alc. was added 42 g. II (R = Me) followed by 20.4 ml. formamide. The solution was heated for 3 hrs. After cooling the Na salt of 4,6-dihydroxypyrimidine was filtered off, washed with absolute alc., and dried in vacuo at 50°. The crude Na salt (72.4 g.) was added slowly to 314 ml. POCl3 below 30°, followed by 31 ml. PhNMe2. The mixture was heated at 130° for 3 hrs. to give 4,6-dichloro-5-methoxypyrimidine (III), m. 57-8°. Similarly prepared were the following IV (R and b12 given): Et, 102-7°; iso-Pr, 108-13°; Bu, 128-33°. A mixture of 48 g. III and 170 ml. liquid NH3 under N at 20 atm. was shaken in an autoclave overnight to give 82% 4-amino-5-methoxy-6-chloropyrimidine (V), m. 176-8°. The 5-ethoxy, m. 119-20° (MeCN), 5-isopropoxy, m. 139-41° (MeCN), and 5-butoxy, m. 103-4°, analogs were prepared To a solution of 29.4 g. Na in 1 l. MeOH was added 170 g. V and the solution heated 18 hrs. to yield 94% 4-amino-5,6-dimethoxypyrimidine (VI), m. 88-9° (isopropyl ether). Similarly prepared were the following VIa (R, R1, and m.p. given): Me, Et, 64-58°; Me, iso-Pr, 111-12°; Me, Pr, 70-1°; Me, CH2CH:CH2, 41-2°; Me, C10H21, 53-4°; Et, Et, 83-4°; Bu, C10H21, 32-3°; Bu, CH2CH2OCH2Me, 98-9°. To a solution of 62 g. VI in 160 ml. absolute pyridine was added over 3 hrs. 130 g. 4-acetamidobenzenesulfonyl chloride at 3-4° and the solution kept overnight to yield 89.5% VII (R = Me, R1 = OMe, X = Ac), m. 230-1° (HOAc), hydrolysis of which with 2N NaOH gave VII (R = Me, R1 = OMe, X = H), m. 201-2°. The following VII (R = Me) were similarly prepared (R1, X, and m.p. given): EtO, Ac, 201-2°; EtO, H, 170-1°; PrO, Ac, 186-7°; PrO, H, 142-3°; iso-PrO, Ac, 195-7°; iso-PrO, H, 136-7°; MeO, HCO, 194-5°. Also prepared were the following VII (X = H) (R, R1, and m.p. given): Me, OC10H21, 94-6°; Me, OPr-iso, 136-7°; Et, Cl, 215-16°; Et, OMe, 228-9°; Et, OEt, 173-4°; Et, OCH2CH:CH2, 152°; Et, OPr, 162°; Et, OPr-iso, 181-3°; Me, OCH2CH:CH2, 145-6°; iso-Pr, OMe, 193-5°; iso-Pr, OEt, 183-4°; iso-Pr, OPr-iso, 170-1°; Bu, Cl, 172-4°; iso-Pr, OCH2CH:CH2, 146-8°; Bu, OMe, 192-3°; H, OC10H21, 142-4°; Cl, OPr-iso, 172-4°. To a solution of 155 g. Na sulfanilamide in 500 ml. Me2NCHO was added slowly 71.6 g. III at 100°. Work-up gave 82% 4-sulfanilamido-5-methoxy-6-chloropyrimidine (VIII), m. 200-2° (alc.-H2O). To a solution of 5.75 g. Na in 200 ml. allyl alc. was added 31.4 g. VIII to give 4-sulfanilamido-5-methoxy-6-allyloxypyrimidine, m. 145 (BuOAc). To 31 g. VI in 140 ml. absolute pyridine was added 88 g. p-nitrobenzenesulfonyl chloride to give 105 g. 4-[bis(4-nitrophenylsulfonyl)amino]-5,6-dimethoxypyrimidine (IX), m. 216-17° (glacial HOAC). Partial hydrolysis of IX with NaOH in absolute MeOH gave 4-(4-nitrobenzenesulfonamido)-5,6-dimethoxypyrimidine (X), m. 136-8° (MeCN). Treatment of X with Ac2O in absolute pyridine for 3 hrs. on a steam bath gave 4-(N-acetyl-4-nitrobenzenesulfonamido)-5,6-dimethoxypyrimidine (XI), m. 160-2° (MeCN). Reduction of 13 g. XI in 540 ml. HOAc in the presence of 13 g. 5% Pd-C at room temperature gave 8.5 g. 4-(N’-acetylsulfanilamido)-5,6-dimethoxypyrimidine, m. 196-8 (MeCN). The following XII were similarly prepared (R, R1, X, and m.p. given): OMe, C10H21, 4-O2NC6H4SO2, 112-13°; OMe, C10H21, H, 114-15°; OBu, OCH2CH2OEt, 4-O2NC6H4SO2, 124-5°; OBu, OCH2CH2OEt, H, 96-8°.

Monatshefte fuer Chemie published new progress about 5018-38-2. 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, Formula: C5H4Cl2N2O.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Chang, P.; Chiang, Kwei-Che published the artcile< 5-Hydroxypyrimidines. II. Synthesis of 2-substituted 4,5-dihydroxypyrimidines>, Recommanded Product: 5-Hydroxypyrimidin-4(3H)-one, the main research area is .

V reacts with HCO2Et gives PhCH2OCH(CHO)CO2Et (X), which condenses with various amidines [RC(:NH)NH2] to 2-R-substituted-5-benzyloxy-4-hydroxypyridines (XI, R), converted by H in the presence of Pd to XII(R). [N:CR.N:C(OH).C(OCH2Ph):CH (XI) and N:CR.N:C(OH).C(OH):CH (XII) are designated by the Roman numeral, followed by R.] XI and XII are stable, high-melting solids, the latter giving the same pos. color tests as III (except that the FeCl3-NH3 colors are different), and reducing 2,6-dichlorophenolindophenol rapidly. When a suspension of NaOMe (from 2.8 g. powd. Na and 10 ml. anhydrous MeOH in 100 ml. dry Et2O) is treated with a 20 g. V and 14 g. HCO2Et with stirring at room temperature during 2 hrs., and stirred 4 hrs. more, the mixture turns from light to orange yellow and a white amorphous solid seps.; after 2 days, 40 ml. H2O, then 12 ml. dilute HOAc are added, the Et2O layer is dried, distilled, and the fraction b1 110-33° or b4 140-53° redistilled, giving 79% X, b1 128-30°, b4 149°, n20D 1.5200, which turns blue-violet with FeCl3. No X is obtained with powd. Na used directly, and solutions of Na in MeOH or EtOH give only 15-20% X. Urea (1.2 g.) added to 0.92 g. Na in 30 ml. anhydrous EtOH, 4.5 g. X stirred in during 1 hr. at room temperature, the mixture heated 4 hrs. on steam, cooled, the solids dissolved by addition of H2O, and the mixture acidified with 6 ml. HOAc gives 70% XI(OH), m. 283° (20% aqueous HOAc)(decomposition). X and IX at room temperature give 78% XI(NH2), m. 243° (20% aqueous HOAc) (decomposition); X and MeC(:NH)NH2.HCl (at 60°) give 93% XI(Me), fine needles from H2O, m. 186°; and NH2CSNH2 [or NH2C(:NH)SEt.HBr, loss of Et occurring during the condensation] and X (at room temperature) give 92% XI(SH), long needles from EtOH, m. 225-6° (decomposition). XI(SEt), m. 189-90°, is obtained by adding 2 ml. EtBr to 0.5 g. XI(SH) in 15 ml. 10% NaOH, heating 3 hrs. on steam, cooling, acidifying with dilute HCl, and recrystallizing the precipitate from EtOH, yield 53.6%. Boiling XI(SH or SEt) in dilute NH4OH with Raney Ni yields XI(H) [83% from XI(SH)], needles, m. 98-9°. Hydrogenation of XI(OH) (0.5 g.) in 30 ml. 5% NaOH containing Pd at room temperature and atm. pressure required 30 min.; acidification of the filtered mixture precipitated XII(OH) (isobarbituric acid), m. 310° (decomposition) (from H2O), yield quant.; addition of XII(OH) to 5% AgNO3 results in immediate precipitation of black metallic Ag. Hydrogenation of XI(NH2) (in HCO2H) gives a quant. yield of XII(NH2) unmelted at 340°. Similarly, XI(Me) is converted to XII(Me), m. 312-13° (decomposition), and XI(H) is reduced to XII(H), m. 268-9° (decomposition). While XII(OH) (like III) gives a blue-violet color on treatment with 1% FeCl3 and a few drops of concentrated NH4OH, XII (R = NH2, H, and Me) give brown colors.

Scientia Sinica (English Edition) published new progress about Color reaction. 15837-41-9 belongs to class pyrimidines, and the molecular formula is C4H4N2O2, Recommanded Product: 5-Hydroxypyrimidin-4(3H)-one.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Prabhakar, Virupakshi; Kondra, Sudhakar Babu; Maddula, Srinivasula Reddy; Parandhama, G.; Latha, J. published the artcile< Synthesis, structural elucidation of novel thieno [2,3-d] pyrimidine core unit containing 1,2,4-triazoles and thiophenes as potent antimicrobial activity>, Name: 2,4-Dichlorothieno[2,3-d]pyrimidine, the main research area is thiophenylboronic acid chloro arylthienotriazolopyrimidine Suzuki coupling; thiophenyl arylthienotriazolopyrimidine preparation antibacterial antifungal activity SAR.

Several new thieno[2,3-d]pyrimidine derivatives 3-substituted phenyl-5-(thiophen-2-yl)thieno[3,2-e] [1,2,4]triazolo[4,3-c]pyrimidines I [R = Ph, 3-pyridyl, 1H-indol-2-yl, etc.] were synthesized starting from thieno[2,3-d]pyrimidine-2,4-diol. The characterization of the newly synthesized compounds I was established by IR, 1H NMR, 13C NMR and mass spectral anal. The final compounds I were screened for their antibacterial activity against Bacillus subtilis and Staphylococcus aureus from Gram pos. group of bacteria and Escherichia coli and Klebsiella pneumonia from Gram neg. group of bacteria and antifungal activity against Candida albicans and Aspergillus flavus. Antibacterial and antifungal activities were evaluated and compared with the standard drugs. From antibacterial and antifungal activity screening results, it was observed that compounds I [R = 3-pyridyl, 1H-indol-2-yl, 4-F3CC6H5] possessed good activity.

Organic Chemistry: Current Research published new progress about Antibacterial agents. 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Name: 2,4-Dichlorothieno[2,3-d]pyrimidine.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Angst, Daniela; Gessier, Francois; Janser, Philipp; Vulpetti, Anna; Walchli, Rudolf; Beerli, Christian; Littlewood-Evans, Amanda; Dawson, Janet; Nuesslein-Hildesheim, Barbara; Wieczorek, Grazyna; Gutmann, Sascha; Scheufler, Clemens; Hinniger, Alexandra; Zimmerlin, Alfred; Funhoff, Enrico G.; Pulz, Robert; Cenni, Bruno published the artcile< Discovery of LOU064 (Remibrutinib), a Potent and Highly Selective Covalent Inhibitor of Bruton's Tyrosine Kinase>, Synthetic Route of 5018-38-2, the main research area is LOU064 remibrutinib Bruton tyrosine kinase inhibitor autoimmune diseases antiinflammatory.

Bruton’s tyrosine kinase (BTK), a cytoplasmic tyrosine kinase, plays a central role in immunity and is considered an attractive target for treating autoimmune diseases. The use of currently marketed covalent BTK inhibitors is limited to oncol. indications based on their suboptimal kinase selectivity. We describe the discovery and preclin. profile of LOU064 (remibrutinib, 25), a potent, highly selective covalent BTK inhibitor. LOU064 exhibits an exquisite kinase selectivity due to binding to an inactive conformation of BTK and has the potential for a best-in-class covalent BTK inhibitor for the treatment of autoimmune diseases. It demonstrates potent in vivo target occupancy with an EC90 of 1.6 mg/kg and dose-dependent efficacy in rat collagen-induced arthritis. LOU064 is currently being tested in phase 2 clin. studies for chronic spontaneous urticaria and Sjoegren’s syndrome.

Journal of Medicinal Chemistry published new progress about Anti-inflammatory agents. 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, Synthetic Route of 5018-38-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Suwal, Sujit; Rahman, Mahmuda; O’Brien, Gregory; Karambizi, Victoire G.; Wrotny, Matthew; Scott Goodman, M. published the artcile< Chemo-selective syntheses of N-t-boc-protected amino ester analogs through Buchwald-Hartwig amination>, Recommanded Product: Ethyl 2-chloropyrimidine-5-carboxylate, the main research area is amino ester preparation chemoselective; heterocyclic halo ester amine Buchwald Hartwig amination.

Synthesis of N-protected amino esters, e.g., I is achieved via a chemo-selective Buchwald Hartwig cross-coupling reaction using PEPPSI-IPr Pd-catalyst. Nearly two dozen functionally and structurally diverse mols. are created by individually cross-coupling eight II (R = Me, Et; Y = CH, N; X = Cl, Br) and three different secondary amines, e.g., tert-Bu piperazine-1-carboxylate. It was the observed that product formation is more facile in those heterocyclic esters II where nitrogen is present ortho to the halo substituent in the heteroaromatic ring. Based on this observation, a possible intermediate step in the cross-coupling cycle is proposed, where the nitrogen electron lone pair in the heterocycle may play an important role leading to a higher reaction yield.

New Journal of Chemistry published new progress about Amino esters Role: SPN (Synthetic Preparation), PREP (Preparation). 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Recommanded Product: Ethyl 2-chloropyrimidine-5-carboxylate.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Beck, Hartmut; Jeske, Mario; Thede, Kai; Stoll, Friederike; Flamme, Ingo; Akbaba, Metin; Ergueden, Jens-Kerim; Karig, Gunter; Keldenich, Joerg; Oehme, Felix; Militzer, Hans-Christian; Hartung, Ingo V.; Thuss, Uwe published the artcile< Discovery of Molidustat (BAY 85-3934): A Small-Molecule Oral HIF-Prolyl Hydroxylase (HIF-PH) Inhibitor for the Treatment of Renal Anemia>, HPLC of Formula: 5018-38-2, the main research area is diheteroaryldihydropyrazolone preparation HIF prolyl hydroxylase inhibitor kidney disease anemia; molidustat BAY3934 preparation HIF prolyl hydroxylase inhibitor kidney anemia; BAY 85-3934; HIF-PH; inhibitors; metalloenzymes; molidustat.

Small-mol. inhibitors of hypoxia-inducible factor prolyl hydroxylases (HIF-PHs) are currently under clin. development as novel treatment options for chronic kidney disease (CKD) associated anemia. Inhibition of HIF-PH mimics hypoxia and leads to increased erythropoietin (EPO) expression and subsequently increased erythropoiesis. Herein the authors describe the discovery, synthesis, structure-activity relationship (SAR), and proposed binding mode of novel 2,4-diheteroaryl-1,2-dihydro-3H-pyrazol-3-ones as orally bioavailable HIF-PH inhibitors for the treatment of anemia. High-throughput screening of the authors’ corporate compound library identified BAY-908 as a promising hit. The lead optimization program then resulted in the identification of molidustat (BAY 85-3934), a novel small-mol. oral HIF-PH inhibitor. Molidustat is currently being investigated in clin. phase III trials as molidustat sodium for the treatment of anemia in patients with CKD.

ChemMedChem published new progress about Anemia (chronic kidney disease associated). 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, HPLC of Formula: 5018-38-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Rosemeyer, Helmut; Kaiser, Klaus; Seela, Frank published the artcile< Dextran-linked 7-deazaguanine - a polymer-bound inhibitor of xanthine oxidase>, Related Products of 84955-32-8, the main research area is xanthine oxidase deazaguanine dextran inhibitor; immobilized deazaguanine xanthine oxidase inhibition.

Dextran-linked 7-deazaguanine as well as 7-deazahypoxanthine and allopurinol derivatives were prepared by carbodiimide condensation of the 2-carboxyethyl intermediates with N-(6-aminohexyl)carbamoylmethylated dextran T80. The dextran-linked bases are degradable by endo-dextranase (EC 3.2.1.11) as demonstrated by time-dependent viscosity measurements. Monomeric as well as polymer-linked purine analogs were tested as inhibitors of xanthine oxidase (EC 1.2.3.1) from cow’s milk. Whereas the allopurinol- and 7-deazahypoxanthine derivatives no longer bind to the enzyme, the 7-deazaguanine derivatives are strong competitive inhibitors of xanthine oxidase even in the polymer-linked state.

International Journal of Biological Macromolecules published new progress about Enzyme kinetics. 84955-32-8 belongs to class pyrimidines, and the molecular formula is C7H8N4O, Related Products of 84955-32-8.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Fun, Hoong-Kun; Yeap, Chin Sing; Chidan Kumar, C. S.; Yathirajan, H. S.; Siddegowda, M. S. published the artcile< 4,6-Dichloro-5-methoxypyrimidine>, SDS of cas: 5018-38-2, the main research area is crystal structure dichloromethoxypyrimidine; mol structure chloromethoxypyrimidine; pyrimidine dichloromethoxy crystal mol structure.

The mol. of 4,6-dichloro-5-methoxypyrimidine, C5H4Cl2N2O, is close to being planar (root-mean-square deviation = 0.013 Å), apart from the C atom of the methoxy group, which deviates by 1.082(2) Å from the mean plane of the other atoms. In the crystal, short Cl···N contacts [3.0940(15) and 3.1006(17) Å] generate a 3-dimensional framework. Crystallog. data are given.

Acta Crystallographica, Section E: Structure Reports Online published new progress about Crystal structure. 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, SDS of cas: 5018-38-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Anderson, Neal G.; Ary, Thomas D.; Berg, James L.; Bernot, Peter J.; Chan, Yeung Y.; Chen, Chien-Kuang; Davies, Merrill L.; DiMarco, John D.; Dennis, Ronald D.; Deshpande, Rajan P.; Do, Hoang D.; Droghini, Roberto; Early, William A.; Gougoutas, Jack Z.; Grosso, John A.; Harris, John C.; Haas, Oscar W.; Jass, Paul A.; Kim, Daniel H.; Kodersha, Gus A.; Kotnis, Atul S.; LaJeunesse, Jean; Lust, David A.; Madding, Gary D.; Modi, Sandeep P.; Moniot, Jerome L.; Nguyen, Andrew; Palaniswamy, Venkatapuram; Phillipson, Douglas W.; Simpson, James H.; Thoraval, Dominique; Thurston, David A.; Tse, Kai; Polomski, Robert E. published the artcile< Process Development of 5-Fluoro-3-[3-[4-(5-methoxy-4-pyrimidinyl)-1- piperazinyl]propyl]-1H-indole Dihydrochloride>, SDS of cas: 5018-38-2, the main research area is fluoromethoxy pyrimidinyl piperazinylpropyl indole dihydrochloride synthesis; antidepressant fluoromethoxypyrimidinyl piperazinylpropyl indole dihydrochloride preparation.

5-Fluoro-3-[3-[4-(5-methoxy-4-pyrimidinyl)-1-piperazinyl]propyl]-1H-indole dihydrochloride (1) facilitates 5-HT neurotransmission and was an antidepressant drug candidate. The development of a safe, rugged process for the large-scale, chromatog.-free preparation of this compound is described. The main areas of optimization included a Fischer indole synthesis, preparation and chlorination of a monohydroxypyrimidine, and coupling of the resultant fragments to prepare the drug substance.

Organic Process Research & Development published new progress about Antidepressants. 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, SDS of cas: 5018-38-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia