Pyrimidines

Application of 2227-98-7, 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. 2227-98-7, name is 4-Aminopyrrolo[3,2-d]pyrimidine. A new synthetic method of this compound is introduced below.

[0065] (4S)-4-{[l-(Triphenylmethyl)-lH-imidazol-4-yl]methyl}-l,3-oxazolidin-2-one or (4S)-4-{[l-(triphenylmethyl)-lH-imidazol-5-yl]methyl}-l,3-oxazolidin-2-one (P.l). A modified literature procedure [Madrigal, et al.14] was followed. (5)-Histidinol dihydrochloride (0.500 g, 2.34 mmol) and diethyl carbonate (2.86 mL, 23.61 mmol) were stirred together in ethanol (24 mL), then sodium methoxide in methanol solution (25%, 1.6 mL, 7.0 mmol) added. The mixture was heated under reflux for 72 h then the solvent was evaporated and the residue chromatographed on silica gel (CHCl3-MeOH-28% aq. NH4OH, 9: 1:0.1) to give (45)-4-(lH-imidazol-4-ylmethyl)-l,3-oxazolidin-2-one as a colourless solid (0.26 g, 1.56 mmol, 90 – 95% pure). XH NMR (500 MHz, CD3OD): delta 7.61 (d, J = 1.0 Hz, 1H), 6.93 (s, 1H), 4.45-4.40 (m, 1H), 4.18-4.12 (m, 2H), 2.86 (dd, J= 14.7, 4.8 Hz, 1H), 2.80 (dd, J= 14.8, 6.1 Hz, 1H). It was dissolved in DMF (4 mL) then triethylamine (0.42 mL, 3.00 mmol) and trityl chloride (0.489 g, 1.70 mmol) were added. The mixture was stirred for 60 h at rt then diluted with Et20 (60 mL) and the mixture washed with H20 (4 x 5mL), brine (5 mL), dried and the solvent evaporated. The residue was chromatographed on silica gel (gradient of 0 – 5% MeOH in EtOAc) to give P.l as a colourless foam (0.520 g, 54%). XH NMR (500 MHz, CD3OD): delta 7.41 (d, J = 1.4 Hz, 1H), 7.39-7.34 (m, 9H), 7.16-7.1 1 (m, 6H), 6.82 (m, 1H), 4.39 (t, J = 8.4 Hz, 1H), 4.19-4.11 (m, 2H), 2.78 (dd, J = 14.6, 4.9 Hz, 1H), 2.73 (dd, J = 14.6, 6.1 Hz, 1H). 13C NMR (125.7 MHz, CD3OD, centre line delta 49.0): delta 162.1 (C), 143.6 (C x 3), 139.8 (CH), 136.6 (C), 130.9 (CH), 129.32 (CH), 129.27 (CH), 121.6 (CH), 76.9 (C), 70.4 (CH2), 53.4 (CH), 33.9 (CH2). ESI-HRMS calcd for C26H23N3Na02+, (M+Na)+, 432.1683, found 432.1677. [0066] (2S)-2-Amino-3-[l-(triphenylmethyl)-lH-imidazol-4-yl]propan-l-ol or (2S)-2- amino-3-[l-(triphenylmethyl)-lH-imidazol-5-yl]propan-l-ol (P.2). Compound P.l (0.510 g, (0109) I .25 mmol) was dissolved in 2-propanol (7 mL) and potassium hydroxide (2 M, 3 mL, 6 mmol) added. The mixture was heated at 80 C for 6 h then silica gel was added to absorb all the solvent then the solvent was evaporated and the residue chromatographed on silica gel (CHCl3-MeOH-28% aq. NH4OH, 9: 1 :0.1) to give P.2 as a colourless gum (0.478 g, 100%). XH NMR (500 MHz, CD3OD): delta 7.40 (d, J = 1.4 Hz, 1H), 7.38-7.34 (m, 9H), 7.18-7.13 (m, 6H), 6.75 (m, 1H), 3.52 (dd, J= 10.9, 4.5 Hz, 1H), 3.35 (dd, J = 10.9. 6.8 Hz, 1H), 3.09-3.03 (m, 1H), 2.65 (dd, J = 14.4, 6.0 Hz, 1H), 2.50 (dd, J = 14.4, 7.4 Hz, 1H). 13C NMR (125.7 MHz, CD3OD, centre line delta 49.0): delta 143.7 (C), 139.7 (CH), 139.2 (C), 130.8 (CH), 129.3 (CH), 129.2 (CH), 121.0 (CH), 76.8 (C), 66.7 (CH2), 53.8 (CH), 33.0 (CH2). ESI-HRMS calcd for C25H26N30+, (M+H)+, 384.2071, found 384.2068. [0067] (2S)-2-[({4-Amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl}methyl)amino]-3-[l- (triphenylmethyl)-lH-imidazol-4-yl]propan-l-ol or (2S)-2-[({4-amino-5H-pyrrolo[3,2- d]pyrimidin-7-yl} methyl)amino] -3 – [ 1 -(triphenylmethyl)- 1 H-imidazol-5-yl]propan- 1 -ol (P.3). Compound P.2 (0.200 g, 0.52 mmol), 9-deazaadenine (0.070 g, 0.52 mmol) and aq. formaldehyde solution (37%, 0.051 mL, 0.68 mmol) were heated at 70 C in tert-butanol (3 mL) forl6 h. Silica gel was added to absorb all the solvent then the solvent was evaporated and the residue chromatographed on silica gel (10% 7M NH3/MeOH-CHCl3) to give P.3 as a colourless foam (0.101 g, 37%). XH NMR (500 MHz, CD3OD): delta 8.03 (s, 1H), 7.39 (s, 1H), 7.35 (d, J = 1.3 Hz, 1H), 7.33-7.29 (m, 9H), 7.12-7.08 (m, 6H), 6.75 (d, J = 1.2 Hz, 1H), 3.96 (d, J = 13.7 Hz, 1H), 3.93 (d, J = 13.6 Hz, 1H), 3.61 (dd, J = 1 1.3, 4.8 Hz, 1H), 3.49 (dd, J = (0111) I I.3, 6.1 Hz, 1H), 3.02-2.97 (m, 1H), 2.72 (dd, J = 14.5, 6.5 Hz, 1H), 2.69 (dd, J = 14.5, 6.7 Hz, 1H). C NMR (125.7 MHz, CD3OD, centre line delta 49.0): delta 152.0 (C), 150.8 (CH), 146.6 (C), 143.7 (C x 3), 139.5 (CH), 139.2 (C), 130.8 (CH), 129.24 (CH), 129.20 (CH), 128.9 (CH), 121.2 (CH), 115.4 (C), 114,8 (C), 76.8 (C), 64.3 (CH2), 59.4 (CH), 41.3 (CH2), 30.7 (CH2). ESI-HRMS calcd for C32H32 70+, (M+H)+, 530.2663, found 530.2666. [0068] (2S)-2-[({4-Amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl}methyl)amino]-3-(lH- imidazol-4-yl)propan-l-ol (PA). Trifluoroacetic acid (0.6 mL, 8 mmol) was added to a stirred solution of P.3 (0.100 g, 0.19 mmol) and triethylsilane (0.090 mL, 0.57 mmol) in CH2CI2 (3 mL). After 2 h, the solvent was evaporated and the residue dissolved in MeOH and the solvent evaporated (3 x). The residue was again dissolved in MeOH, silica gel added and the solvent evaporated. Flash chromatography on silica gel (CHCl3-MeOH-28% aq. NH4OH, 7:2.5:0.5) gave P.4 as a colourless gum which crystallized on standing (0.050 g, 92%). XH NMR (500 MHz, CD3OD): delta 8.14 (s, 1H), 7.52 (d, J= 0.9 Hz, 1H), 7.42 (s, 1H), 6.80 (s, 1H), 4.01 (d, J= 13.6 Hz, 1H), 3.98 (d, J= 13.6 Hz, 1H), 3.63 (dd, J= 11.3, 4.7 Hz, 1H), 3.50 (dd, (0113) J = 11.3, 5…

At the same time, in my other blogs, there are other synthetic methods of this type of compound,2227-98-7, 4-Aminopyrrolo[3,2-d]pyrimidine, and friends who are interested can also refer to it.

Reference:
Patent; ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIVERSITY; SCHRAMM, Vern, L.; CLINCH, Keith; GULAB, Shivali, Ashwin; WO2015/123101; (2015); A1;,
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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.4316-97-6, name is 4,6-Dichloro-5-methylpyrimidine, molecular formula is C5H4Cl2N2, molecular weight is 163.01, as common compound, the synthetic route is as follows.HPLC of Formula: C5H4Cl2N2

To a solution OF 4-HYDROXY-PIPERIDINE-1-CARBOXYLIC acid isopropyl ester (6.26 g, 33.4 mmol) and 4,6-dichloro-5-methyl-pyrimidine (5.45 g, 33.4 mmol) in 100 mL THF, 1M potassium TERT- butoxide in THF (40 mL, 40 mmol) were added slowly by syringe pump. After 1 hour, everything had been added and mixture was concentrated. Residue was extracted with methylene chloride and water. Organic phases were dried over magnesium sulfate, filtered, and concentrated to give 4- (6- CHLORO-5-METHYL-PYRIMIDIN-4-YLOXY)-PIPERIDINE-1-CARBOXYLIC acid isopropyl’ester as a pale yellow solid (10.3 g, 98%). H NMR (CDC13, 400 MHz) 8 1.22-1. 24 (d, 6H), 1.74-1. 81 (M, 2H), 1.95-2. 04 (M, 2H), 2.24 (s, 3H), 3.40-3. 45 (M, 2H), 3.74-3. 81 (M, 2H), 4.90-4. 98 (M, 1H), 5.31-5. 37 (M, 1H), 8.40 (s, 1H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound,4316-97-6, 4,6-Dichloro-5-methylpyrimidine, and friends who are interested can also refer to it.

Reference:
Patent; ARENA PHARMACEUTICALS, INC.; WO2005/7647; (2005); A1;,
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Related Products of 5018-38-2, 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. 5018-38-2, name is 4,6-Dichloro-5-methoxypyrimidine, molecular formula is C5H4Cl2N2O, 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.

Example 3.4 Preparation of 4-(6-Chloro-5-methoxy-pyrimidin-4-yloxy)-piperidine-1-carboxylic Acid Isopropyl Ester A solution of 4-hydroxy-piperidine-1-carboxylic acid isopropyl ester (71.0 g, 380 mmol) and 4,6-dichloro-5-methoxypyrimidine (71.6 g, 400 mmol) in anhydrous THF (1 L) was cooled to 5 C. under N2. A solution of potassium t-butoxide (1.0 M in THF, 380 mL, 380 mmol) was added dropwise over 1 h. The reaction temperature was kept under 10 C. during addition. The reaction mixture was stirred at 5-10 C. for 1 h, quenched with saturated NH4Cl (200 mL), and diluted with ether (1 L) and water (1 L). The aqueous phase was separated and discarded. The organic extract was washed with brine (800 mL), dried over MgSO4, and then concentrated. The residue was dissolved in hexane (400 mL) and filtered over Celite to remove a small amount of brown solid. The solvent was removed from the filtrate to afford a pale amber oil which gradually crystallized to give the title compound (130 g, 98.6% yield) as a pale amber solid. Exact Mass calculated for C14H20ClN3O4: 329.1. Found: LCMS m/z=330.2 (M+H+); 1H NMR (400 MHz, CDCl3) delta 1.25 (d, J=6.2 Hz, 6H), 1.82 (m, 2H), 2.02 (m, 2H), 3.40 (m, 2H), 3.80 (m, 2H), 3.91 (s, 3H), 4.95 (m, 1H), 5.39 (m, 1H), 8.27 (s, 1H).

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 5018-38-2, 4,6-Dichloro-5-methoxypyrimidine.

Reference:
Patent; ARENA PHARMACEUTICALS, INC.; US2009/286816; (2009); A1;,
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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.5399-92-8, name is 4-Chloro-1H-pyrazolo[3,4-d]pyrimidine, molecular formula is C5H3ClN4, molecular weight is 154.5571, as common compound, the synthetic route is as follows.Quality Control of 4-Chloro-1H-pyrazolo[3,4-d]pyrimidine

To a solution of 4-chloro-lH-pyrazolo[3,4-^pyrimidine (J. Amer. Chem. SQC. 1957, 79, 6407-6413) (51 mg, 0.33 mmol) in ethanol (2 ml) was added triethylamine (100 mul, 0.72 mmol) and 4-(N-Boc-aminomethyl)piperidine (87 mg, 0.41 mmol). The solution was heated at 80 C for 3 hours, and then cooled to room temperature. The solution was evaporated to dryness and the residue purified by recrystallisation (isopropanol) to yield the intermediate NH-BOC protected product (33 mg, 30% yield).To the intermediate NH-BOC protected product (32 mg, 0.096 mmol) was added HCl (1 ml, 4M solution in dioxane, 4 mmol). The suspension was stirred at room temperature for 1 hour, and then diluted with diethyl ether (4 ml). The ethereal layer was discarded and the solid washed with a further portion of diethyl ether (2 ml). The ethereal layer was again discarded, and the resultant solid dried under high vacuum. The free base was liberated by dissolution of this material in methanol, loading onto an acidic resin SCX-2 cartridge, and elution from the cartridge with ammonia in methanol to give the title compound (21 mg, quantitative). LC/MS Rt 0.86 [M+H]+233

At the same time, in my other blogs, there are other synthetic methods of this type of compound,5399-92-8, 4-Chloro-1H-pyrazolo[3,4-d]pyrimidine, and friends who are interested can also refer to it.

Reference:
Patent; ASTEX THERAPEUTICS LIMITED; THE INSTITUTE OF CANCER RESEARCH: ROYAL CANCER HOSPITAL; CANCER RESEARCH TECHNOLOGY LIMITED; WO2006/46023; (2006); A1;,
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Adding a certain compound to certain chemical reactions, such as: 302964-08-5, 2-((6-Chloro-2-methylpyrimidin-4-yl)amino)-N-(2-chloro-6-methylphenyl)thiazole-5-carboxamide, 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, 302964-08-5, blongs to pyrimidines compound. Recommanded Product: 302964-08-5

Example 25; Procedure for the Preparation of Dasatinib Form T1E2-1 (Hemi-Ethanolate)A mixture of compound 1 (0.45 g, 1.14 mmol), N-(2-hydroxyethyl)piperazine (0.30 g, 2.30 mmol) and N-ethyldiisopropylamine (0.30 ml, 1.75 mmol) in DMSO (5 ml) was stirred at 60-65 C. for 2 hours. EtOH (30 ml) was slowly added at this temperature followed by H2O (40 ml). The solution was slowly cooled to 0-5 C. The product was filtered off and washed with ethanol (5 ml) and dried on the filter. Yield: 0.38 g.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,302964-08-5, its application will become more common.

Reference:
Patent; SIMO, Ondrej; Filipcik, Jiri; Martaus, Alexandr; Jegorov, Alexandr; Gavenda, Ales; Aronhime, Judith; Vraspir, Pavel; Koltai, Tamas; Faustmann, Jiri; Gabriel, Roman; US2009/118297; (2009); A1;,
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Reference of 90213-67-5 , The common heterocyclic compound, 90213-67-5, name is 2,4-Dichloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine, molecular formula is C7H5Cl2N3, 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.

General procedure: A solution of 1 (400 mg, 1.98 mmol) in anhydrous toluene (10 mL)was flushed with Ar and Pd(PPh3)2Cl2 (14.0 mg, 0.02 mmol), AsPh3(24.5 mg, 0.08 mmol) and the corresponding (arylethynyl)tributylstannane(2.38 mmol) were added. The mixture was stirred under Ar at 80 C for 2 h. After cooling, the mixture was poured into aq K2CO3 solution (0.5 M, 25 mL) containing CsF (50 mg), stirred for 30 min and then extracted with CHCl3. The extract was dried over Na2SO4, filtered and the CHCl3 removed on a rotary evaporator. The residue was purified by column chromatography (CHCl3) to afford 2a-h.

The synthetic route of 90213-67-5 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Bucevicius, Jonas; Tumkevicius, Sigitas; Synthesis; vol. 47; 14; (2015); p. 2100 – 2112;,
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Adding a certain compound to certain chemical reactions, such as: 776-53-4, Ethyl 4-amino-2-(methylthio)pyrimidin-5-carboxylate, 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, category: pyrimidines, blongs to pyrimidines compound. category: pyrimidines

To a suspension of LiA1H4 (10.53 g, 277.0 mmol, 2.2 equiv) in THF (500 mL) was added drop wise ethyl 4-amino-2-(methylthio)pyrimidine-5-carboxylate (26.8 g, 126.0 mmol, 1.0 equiv)10 in THF (500 mL) at 0C. The resulting mixture was stirred at 0C for 5 h. The reaction was quenched with 15% NaOH solution. The mixture was stirred for 1 h. The white precipitate was removed by filtration, washing with EtOAc. The filtrate was concentrated under vacuum to give 22 g (crude) of (4-amino-2-(methylthio)pyrimidin-5-yl)methanol as a white solid.

The synthetic route of 776-53-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PRINCIPIA BIOPHARMA, INC.; VERNER, Erik; BRAMELD, Kenneth Albert; WO2015/120049; (2015); A1;,
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Reference of 1445-39-2, 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. 1445-39-2, name is 2-Amino-5-iodopyrimidine, molecular formula is C4H4IN3, 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.

646 mg (corresponding to 3.0 mmol) of 2-bromo-4′-hydroxyacetophenone and 668 mg (corresponding to 3.0 mmol) of 2-amino-5-iodopyrimidine were dissolved in 20 mL of acetonitrile. The resulting solution was refluxed in an oil bath at 110C for 8 hours. After the completion of the reaction, the reaction solution was cooled down to room temperature, and precipitates were filtered and recovered. The precipitates were washed with acetonitrile and dried under reduced pressure. The resulting crude crystals were suspended in a mixed solution of 10 mL of water and 10 mL of methanol. Then, about 15 mL of a saturated sodium hydrogencarbonate solution was added thereto, and the mixture was sonicated for 3 minutes using an ultrasonic washing machine. Precipitates were filtered and recovered from the resulting mixture, sufficiently washed with water, and dried under reduced pressure, to obtain 737 mg (corresponding to 2.19 mmol) of 2-(4′-hydroxyphenyl)-6-iodoimidazo[1,2-a]pyrimidine (Fig. 1-8, Step 2).

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 1445-39-2, 2-Amino-5-iodopyrimidine.

Reference:
Patent; NIHON MEDI-PHYSICS CO., LTD.; EP2019103; (2009); A1;,
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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 1194-21-4, name is 2-Amino-6-chloropyrimidin-4(3H)-one. This compound has unique chemical properties. The synthetic route is as follows. SDS of cas: 1194-21-4

PREPARATION 7 2-Amino-5-iodo-6-chloro-4-pyrimidinol To 1.45 grams (10.0 millimoles) of 6-chloro-isocytosine is added 15 ml. of dimethylformamide (DMF) and 2.27 grams (10.08 millimoles) of N-iodosuccinimide. With protection from external moisture, the mixture is heated on a steam bath for one-hour hour. The resulting brownish red solution is allowed to stand overnight at room temperature with continued exclusion of moisture. The solution is evaporated under reduced pressure and the residual solid azeotroped once with ethanol in vacuo. The resulting solid is triturated with glacial acetic acid. The insoluble solid is collected, washed with a small volume of glacial acetic acid, then with acetone. The solid is re-triturated with glacial acetic acid, collected, washed with acetone and air-dried. Yield, 1.50 g. Evaporation of the combined filtrate in vacuo, trituration of the residue with water, then acetone gives, after collecting and drying, 970 mg. of second-crop material. The first-crop material is crystallized twice from glacial acetic acid to give 540 mg. of 2-amino-5-iodo-6-chloro-4-pyrimidinol which decomposes at >270, has lambdamax0.1N NaOh 236 nm. (epsilon9,150); 285 nm. (epsilon6,200) and the infrared absorption below. NH/CH, 3380, 3300, 3190, 3130; O=O/C=C/C=N/NH deformation, 1670v.s., 1580, 1540; C–N/Other, 1320, 1215, 1010; Other, 910, 755 cm-1. Analysis Calcd. for: C4 H3 CllN3 O: C, 17.73; H, 1.11; Cl, 13.08; l, 46.83; N, 15.51. Found: C, 18.51; H, 2.24; Cl, 13.38; l, 46.50; N, 14.70.

With the rapid development of chemical substances, we look forward to future research findings about 1194-21-4.

Reference:
Patent; The Upjohn Company; US3932617; (1976); A;,
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Application of 57489-77-7, 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 57489-77-7, name is 5,7-Dichloropyrazolo[1,5-a]pyrimidine. This compound has unique chemical properties. The synthetic route is as follows.

General procedure: To a well stirred 8-aminoquinoline (1 mmol) indry DMF (5 mL), sodium hydride (1.2 mmol, 60% in mineral oil) was added at 0 C.After 10 min stirring, the corresponding heterocyclic chloro compound (1.2mmol) was added and stirred for 10 min at rt then heated at 60 C for 5-12 h.Upon completion, the reaction mixture was poured into crushed ice and theresulting solid was filtered, washed with water and dried under vacuum. Thesolid was triturated with methanol and dried under vacuum to afford targetcompound as a solid.

According to the analysis of related databases, 57489-77-7, the application of this compound in the production field has become more and more popular.

Reference:
Article; Kannan, Murugan; Raichurkar, Anandkumar V.; Khan, Fazlur Rahman Nawaz; Iyer, Pravin S.; Bioorganic and Medicinal Chemistry Letters; vol. 25; 5; (2015); p. 1100 – 1103;,
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