With ferric sulfate nonahydrate In water at 80℃; for 24 h;
General procedure: To model the chemical environment on the outer side of thetubular structures, NH2CHO (200 μL) was mixed with thesodium silicate solution (2.0 mL) in the presence of preformedMSH [ZnCl2, FeCl2·4H2O, CuCl2·2H2O, Fe2(SO4)3·9H2O,and MgSO4] (2.0percent w/w) at 80 °C for 24 h. In two selectedcases [FeCl2 and Fe2(SO4)3·9H2O], NH2CHO (200 μL) wasmixed with the sodium silicate solution (2.0 mL) in the presence of selected growing MSH (starting from 2.0percent w/w ofthe corresponding salt’s pellet) at 80 °C for 24 h. For the innerenvironment, NH2CHO (200 μL) was mixed with distilledwater (2.0 mL) in the presence of selected MSH (2.0percent w/w) at80 °C for 24 h. The reaction of NH2CHO (10percent v/v) with thesodium silicate solution (pH 12) without MSH membranes wasalso analyzed under similar experimental conditions. Theproducts were analyzed by gas chromatography associatedwith mass spectrometry (GC-MS) after treatment with N,Nbis-trimethylsilyl trifluoroacetamide in pyridine (620 μL) at 60°C for 4 h in the presence of betulinol (CAS Registry Number473-98-3) as the internal standard (0.2 mg). Mass spectrometrywas performed by the following program: injection temperature280 °C, detector temperature 280 °C, gradient 100 °C for 2min, and 10 °C/min for 60 min. To identify the structure of theproducts, two strategies were followed. First, the spectra werecompared with commercially available electron mass spectrumlibraries such as NIST (Fison, Manchester, U.K.). Second, GCMSanalysis was repeated with standard compounds. Allproducts have been recognized with a similarity index (SI)greater than 98percent compared to that of the reference standards.The analysis was limited to products of ≥1 ng/mL, and theyield was calculated as micrograms of product per startingformamide. For further experimental details, see the SupportingInformation.
General procedure: To model the chemical environment on the outer side of thetubular structures, NH2CHO (200 μL) was mixed with thesodium silicate solution (2.0 mL) in the presence of preformedMSH [ZnCl2, FeCl2·4H2O, CuCl2·2H2O, Fe2(SO4)3·9H2O,and MgSO4] (2.0percent w/w) at 80 °C for 24 h. In two selectedcases [FeCl2 and Fe2(SO4)3·9H2O], NH2CHO (200 μL) wasmixed with the sodium silicate solution (2.0 mL) in the presence of selected growing MSH (starting from 2.0percent w/w ofthe corresponding salt’s pellet) at 80 °C for 24 h. For the innerenvironment, NH2CHO (200 μL) was mixed with distilledwater (2.0 mL) in the presence of selected MSH (2.0percent w/w) at80 °C for 24 h. The reaction of NH2CHO (10percent v/v) with thesodium silicate solution (pH 12) without MSH membranes wasalso analyzed under similar experimental conditions. Theproducts were analyzed by gas chromatography associatedwith mass spectrometry (GC-MS) after treatment with N,Nbis-trimethylsilyl trifluoroacetamide in pyridine (620 μL) at 60°C for 4 h in the presence of betulinol (CAS Registry Number473-98-3) as the internal standard (0.2 mg). Mass spectrometrywas performed by the following program: injection temperature280 °C, detector temperature 280 °C, gradient 100 °C for 2min, and 10 °C/min for 60 min. To identify the structure of theproducts, two strategies were followed. First, the spectra werecompared with commercially available electron mass spectrumlibraries such as NIST (Fison, Manchester, U.K.). Second, GCMSanalysis was repeated with standard compounds. Allproducts have been recognized with a similarity index (SI)greater than 98percent compared to that of the reference standards.The analysis was limited to products of ≥1 ng/mL, and theyield was calculated as micrograms of product per startingformamide. For further experimental details, see the SupportingInformation.
With copper(II) choride dihydrate In water at 80℃; for 24 h;
General procedure: To model the chemical environment on the outer side of thetubular structures, NH2CHO (200 μL) was mixed with thesodium silicate solution (2.0 mL) in the presence of preformedMSH [ZnCl2, FeCl2·4H2O, CuCl2·2H2O, Fe2(SO4)3·9H2O,and MgSO4] (2.0percent w/w) at 80 °C for 24 h. In two selectedcases [FeCl2 and Fe2(SO4)3·9H2O], NH2CHO (200 μL) wasmixed with the sodium silicate solution (2.0 mL) in the presence of selected growing MSH (starting from 2.0percent w/w ofthe corresponding salt’s pellet) at 80 °C for 24 h. For the innerenvironment, NH2CHO (200 μL) was mixed with distilledwater (2.0 mL) in the presence of selected MSH (2.0percent w/w) at80 °C for 24 h. The reaction of NH2CHO (10percent v/v) with thesodium silicate solution (pH 12) without MSH membranes wasalso analyzed under similar experimental conditions. Theproducts were analyzed by gas chromatography associatedwith mass spectrometry (GC-MS) after treatment with N,Nbis-trimethylsilyl trifluoroacetamide in pyridine (620 μL) at 60°C for 4 h in the presence of betulinol (CAS Registry Number473-98-3) as the internal standard (0.2 mg). Mass spectrometrywas performed by the following program: injection temperature280 °C, detector temperature 280 °C, gradient 100 °C for 2min, and 10 °C/min for 60 min. To identify the structure of theproducts, two strategies were followed. First, the spectra werecompared with commercially available electron mass spectrumlibraries such as NIST (Fison, Manchester, U.K.). Second, GCMSanalysis was repeated with standard compounds. Allproducts have been recognized with a similarity index (SI)greater than 98percent compared to that of the reference standards.The analysis was limited to products of ≥1 ng/mL, and theyield was calculated as micrograms of product per startingformamide. For further experimental details, see the SupportingInformation.
Reference：
[1] Chemistry - A European Journal, 2018, vol. 24, # 32, p. 8126 - 8132
6
[ 77287-34-4 ]
[ 51953-18-5 ]
[ 1455-77-2 ]
[ 120-89-8 ]
[ 73-40-5 ]
[ 328-42-7 ]
[ 2491-15-8 ]
[ 110-15-6 ]
[ 71-30-7 ]
[ 120-73-0 ]
[ 144-62-7 ]
[ 113-00-8 ]
[ 127-17-3 ]
[ 66-22-8 ]
[ 66224-66-6 ]
[ 57-13-6 ]
[ 56-40-6 ]
[ 302-72-7 ]
Reference：
[1] Chemistry - A European Journal, 2018, vol. 24, # 32, p. 8126 - 8132
7
[ 71-30-7 ]
[ 74-88-4 ]
[ 1122-47-0 ]
Reference：
[1] European Journal of Medicinal Chemistry, 2009, vol. 44, # 3, p. 1172 - 1179
[2] New Journal of Chemistry, 2010, vol. 34, # 11, p. 2634 - 2642
[3] Journal of Biological Chemistry, 1909, vol. 5, p. 62[4] Chem. Zentralbl., 1908, vol. 79, # II, p. 1265
[5] Patent: US2013/245043, 2013, A1, . Location in patent: Paragraph 0527; 0528; 0529; 0530
8
[ 71-30-7 ]
[ 10504-60-6 ]
[ 1122-47-0 ]
Reference：
[1] Bulletin de la Societe Chimique de France, 1984, vol. 2, # 11-12, p. 431 - 434
9
[ 71-30-7 ]
[ 616-38-6 ]
[ 1122-47-0 ]
[ 6220-49-1 ]
[ 2228-27-5 ]
[ 124210-92-0 ]
Reference：
[1] Zeitschrift fuer Naturforschung, B: Chemical Sciences, 1989, vol. 44, # 7, p. 863 - 865
10
[ 512-56-1 ]
[ 71-30-7 ]
[ 4776-08-3 ]
[ 608-34-4 ]
[ 1122-47-0 ]
[ 6749-87-7 ]
Reference：
[1] Bulletin of the Chemical Society of Japan, 1980, vol. 53, # 1, p. 277 - 278
11
[ 512-56-1 ]
[ 71-30-7 ]
[ 4776-08-3 ]
[ 1122-47-0 ]
[ 6749-87-7 ]
Reference：
[1] Bulletin of the Chemical Society of Japan, 1980, vol. 53, # 1, p. 277 - 278
[2] Bulletin of the Chemical Society of Japan, 1980, vol. 53, # 1, p. 277 - 278
[3] Bulletin of the Chemical Society of Japan, 1980, vol. 53, # 1, p. 277 - 278
12
[ 71-30-7 ]
[ 616-38-6 ]
[ 1122-47-0 ]
[ 6220-49-1 ]
[ 874-14-6 ]
[ 2228-27-5 ]
[ 124210-93-1 ]
[ 124210-92-0 ]
Reference：
[1] Zeitschrift fuer Naturforschung, B: Chemical Sciences, 1989, vol. 44, # 7, p. 863 - 865
Reference：
[1] Synlett, 2002, # 12, p. 2043 - 2044
[2] Canadian Journal of Chemistry, 2007, vol. 85, # 4, p. 302 - 312
15
[ 554-01-8 ]
[ 1123-95-1 ]
[ 71-30-7 ]
[ 65-71-4 ]
Reference：
[1] Chemical Research in Toxicology, 1996, vol. 9, # 4, p. 745 - 750
16
[ 71-30-7 ]
[ 2022-85-7 ]
Yield
Reaction Conditions
Operation in experiment
95.7%
Stage #1: at -15 - 0℃; Inert atmosphere Stage #2: at -20℃; for 4 h; Inert atmosphere
(1) Under nitrogen, the temperature is 0 , the quality of anhydrous hydrogen fluoride was added 1150g 3450g cytosine, at a temperature of -15 deg.] C, into fluorine gas content of 15percent fluorine gas, a mixed gas of nitrogen, flow rate of 40g / h, fluorination reaction; document.write(""); After (2) a reaction for 4 hours in ventilation of nitrogen gas remove excess fluorine gas at -20 reaction of anhydrous hydrogen fluoride was distilled off in vacuo to dryness, water was added 8L, calcium carbonate was added to adjust the pH to 8; document.write(""); (3) The reaction was warmed to 90 deg.] C for 1 hour, filtered hot, 100g activated carbon was added, incubated 90 deg.] C for 0.5 hours and then filtered hot, cooled to 25 deg.] C for 0.5 hours, then cooled to 0 deg.] C, stirred for 1 hour , 5-fluorocytosine was filtered to give a white wet product; document.write(""); (4) the wet product 5-fluorocytosine after 70 deg.] C bake for 16 hours to give 5-fluorocytosine dried. document.write(""); Purity by HPLC and liquid phase titration analysis to analyze the content of 5-fluorocytosine purity and yield the following results: 95.7percent yield, 97.7percent pure.
87.4%
at 20℃; Inert atmosphere
(Figure 1) corning straight channel module 1 (as premix preheat module), corning "heart" microchannel reaction module 6, corning straight channel module 1 (as quenching module) and heat transfer module 8 , And the continuous flow microchannel reaction system is composed according to the reaction flow shown in Fig. The reaction heat transfer medium is made of heat transfer oil. According to the principle of forced heat transfer of microchannel reactor, only two temperature measurement points are set in the inlet and outlet of the reactor. Before the reaction, the microchannel reaction system and the connecting pipeline were treated by dewatering and degreasing respectively. The system and the connecting line were passivated with 5molpercent fluorine and nitrogen gas mixture to carry out the airtightness check of 1.0MPa. The uracil solution (i.e., a mixture of uracil and anhydrous hydrofluoric acid, and the concentration of uracil 7percent) was continuously added to the microchannel reaction system by the 1-liquid chestnut (Fig. 3). With the gas mass flow meter of Fig. 3, A 20 molpercent fluorine-nitrogen mixed gas was continuously added to the microchannel reaction system.Set the heat exchanger temperature 0 ° C, ie the reaction temperature. Set the reaction pressure 0. IMPa. The molar ratio of fluorine gas to uracil was 1.2: 1, and the molar ratio of fluorine gas to uracil was 1.2: 1. The reaction mixture was heated into the "heart-shaped" microchannel reaction module 4 by the microchannel pre-heating module 3 and the fluorine-nitrogen mixed gas was directly introduced into the "heart-shaped" microchannel reaction module 4 through the gas mass flow meter. Heart-shaped "microchannel reaction module 4-9, the fluorine-nitrogen mixture reacts with uracil. The crude reaction product is separated by a gas-liquid separator after quenching the module 10 and then treated by a system and dried to obtain a 5-fluorouracil product. The reaction product was analyzed by liquid chromatography. The results showed that the purity of 5-fluorouracil reached 98.6percent and the product yield was 86.7percent. The same Corning microchannel reactor was used as in Example 1, and the same connection method and control method were used. This example changes the reaction conditions.Set the heat exchanger temperature 20 ° C, ie the reaction temperature. Set the reaction pressure 0.15MPa. The reaction material 2 is a cytosine solution, that is, a mixture of cytosine and hexafluoroisopropanol, the mass concentration of uracil is 3percent and the feed rate is 80 g / min. The raw material 1 is 20 molpercent of the fluorine-nitrogen mixed gas, and the feed rate is 2.90 L / min. The molar ratio of fluorine to cytosine was 1.2: 1. The raw material 2 cytosine solution was pre-heated by the microchannel preheating module 3 into the "heart-shaped" microchannel reaction module 4. The fluorine-nitrogen mixed gas was directly introduced into the microchannel reaction module 4 through the gas mass flow meter, In the channel reaction module 4-9, the fluorine-nitrogen mixture reacts with cytosine. The crude reaction product is separated by a gas-liquid separator after quenching the module 10 and then treated by a system and dried to obtain a 5-fluorocytosine product. The reaction product was analyzed by liquid chromatography, and the purity of 5-fluorocytosine was 99.3percent and the product yield was 87.4percent.
63%
for 1.5 h; Flow reactor; Autoclave
1.0 M cytosine solution in formic acid was introduced at 4.0 mL/h (4.0 mmol/h) while fluorine (10 percent in N2) was introduced at 20 mL/min (5 mmol/h). The reaction was conducted for 90 minutes, the collected fraction was evaporated and the residue was recrystallized from water (7 mL). After filtration, the product was dried under reduced pressure to afford 5-fluorocytosine (0.49 g, 63 percent yield) as a tan powder. M.p.: 295 - 300 °C (decomposes), ([M]+ 129.0337, [M]+ requires: 129.0338); IR (cm"1): 3384, 3092, 2724, 1665, 1624, 1551, 1454, 1216; 1 H NMR (400 MHz, D2O+DCI) 7.83 (1 H, d, 3JHF 4.8 Hz); 19F NMR (400 MHz, D2O+DCI) -169.7 (1 F, d, 3JHF 4.8 Hz); 13C NMR (100 MHz, D2O+DCI): 130.67 (d, 2JCF 29.6 Hz), 135.25 (d, 1JCF 232 Hz), 147.88, 153.65 (d, 2JCF 23.4 Hz); MS (ASAP): 11 1 (37 percent, [M+H-F]+), 129 (8 percent, [M]+), 130 (100 percent, [M+H]+).
Reference：
[1] Patent: CN104326990, 2016, B, . Location in patent: Paragraph 0042-0043
[2] Patent: CN106432099, 2017, A, . Location in patent: Paragraph 0028-0031; 0047-0051
[3] Patent: WO2016/30662, 2016, A1, . Location in patent: Paragraph 00251
[4] Patent: CN107089952, 2017, A, . Location in patent: Paragraph 0036; 0037; 0038; 0039; 0040; 0041; 0042; 0043
17
[ 71-30-7 ]
[ 2022-85-7 ]
Yield
Reaction Conditions
Operation in experiment
66%
for 1.5 h; Flow reactor; Sealed tube
General procedure: 1.0 M cytosine solution in formic acid was introduced at 4.0 mL/h (4.0 mmol/h) while fluorine (10 percent in N2) was introduced at 20 mL/min (5 mmol/h). The reaction was conducted for 90 minutes, the collected fraction was evaporated and the residue was recrystallized from water (7 mL). After filtration, the product was dried under reduced pressure to afford 5-fluorocytosine (0.49 g, 63 percent yield) as a tan powder. M.p.: 295 - 300 °C (decomposes), ([M]+ 129.0337, [M]+ requires: 129.0338); IR (cm"1): 3384, 3092, 2724, 1665, 1624, 1551, 1454, 1216; 1 H NMR (400 MHz, D2O+DCI) 7.83 (1 H, d, 3JHF 4.8 Hz); 19F NMR (400 MHz, D2O+DCI) -169.7 (1 F, d, 3JHF 4.8 Hz); 13C NMR (100 MHz, D2O+DCI): 130.67 (d, 2JCF 29.6 Hz), 135.25 (d, 1JCF 232 Hz), 147.88, 153.65 (d, 2JCF 23.4 Hz); MS (ASAP): 11 1 (37 percent, [M+H-F]+), 129 (8 percent, [M]+), 130 (100 percent, [M+H]+).
Reference：
[1] Patent: WO2016/30662, 2016, A1, . Location in patent: Paragraph 00251; 00273
[2] Organic Process Research and Development, 2017, vol. 21, # 2, p. 273 - 276
18
[ 71-30-7 ]
[ 2022-85-7 ]
Reference：
[1] Journal of Fluorine Chemistry, 1984, vol. 24, p. 355 - 362
19
[ 71-30-7 ]
[ 2240-25-7 ]
Yield
Reaction Conditions
Operation in experiment
95.6%
With N-Bromosuccinimide In N,N-dimethyl-formamide at 15℃; for 1 h; Sonication
The cytosine (55.6g, 0.5mol), N-bromosuccinimide (106.8g, 0 . 6mol) and DMF150mL in added in the reaction bottle, cooling to 15 °C ultrasonic reaction 1h, TLC raw material the reaction is complete, filtering, the filter cake is washed with water (20 ml × 2) washing, drying to obtain 5-bromocytosine (90.9g, 95.6percent).
Reference：
[1] Patent: CN103819412, 2016, B, . Location in patent: Paragraph 0023-0025; 0031-0032; 0037; 0038
[2] Synthesis, 2005, # 7, p. 1103 - 1108
[3] Tetrahedron Letters, 1992, vol. 33, # 50, p. 7779 - 7782
[4] Chemistry Letters, 1987, p. 2311 - 2312
[5] Bulletin of the Chemical Society of Japan, 1989, vol. 62, # 11, p. 3750 - 3751
[6] Journal of Organic Chemistry, 1982, vol. 47, # 6, p. 1018 - 1023
20
[ 71-30-7 ]
[ 51-20-7 ]
[ 2240-25-7 ]
Reference：
[1] Journal of Labelled Compounds and Radiopharmaceuticals, 1994, vol. 34, # 7, p. 603 - 616
21
[ 71-30-7 ]
[ 2240-25-7 ]
Reference：
[1] Journal of the American Chemical Society, 1934, vol. 56, p. 134,138
22
[ 71-30-7 ]
[ 1122-44-7 ]
Yield
Reaction Conditions
Operation in experiment
99%
With N-iodo-succinimide In N,N-dimethyl-formamide for 12.5 h; Sonographic reaction; Inert atmosphere
DMF (50 mL) is added to a mixture of cytosine (8.333 g, 75 mmol) with N-iodosuccinimide (18.562 g, 82.5 mmol) under Ar. The vessel is covered in foil and ultrasonicated for 30 min to disrupt the solid mass at the bottom of the vessel. The mixture is then stirred for an additional 12 h, the still heterogeneous reaction mixture is added to water (150 mL). The insoluble material is collected by filtration, washed with water and dried over P2O5 to give the iodinated heterocycle is a pale tan solid (17.703 g, 99percent). The material is used without further purification.
Reference：
[1] Patent: US7741294, 2010, B1, . Location in patent: Page/Page column 17
[2] European Journal of Organic Chemistry, 2015, vol. 2015, # 32, p. 7160 - 7175
[3] Journal of Medicinal Chemistry, 1983, vol. 26, # 2, p. 152 - 156
[4] Tetrahedron, 2012, vol. 68, # 26, p. 5145 - 5151
[5] Journal of Heterocyclic Chemistry, 2015, vol. 52, # 5, p. 1382 - 1389
[6] Synthesis, 2003, # 7, p. 1039 - 1042
[7] Journal of the American Chemical Society, 2008, vol. 130, # 27, p. 8762 - 8768
[8] Journal of Biological Chemistry, 1906, vol. 1, p. 310[9] Chem. Zentralbl., 1906, vol. 77, # I, p. 1890
[10] Structural Chemistry, 2010, vol. 21, # 1, p. 245 - 254
[11] Molecules, 2017, vol. 22, # 12,
23
[ 71-30-7 ]
[ 108-24-7 ]
[ 14631-20-0 ]
Reference：
[1] Journal of Organic Chemistry, 1991, vol. 56, # 14, p. 4392 - 4397
[2] Journal of Polymer Science, Part A: Polymer Chemistry, 2015, vol. 53, # 9, p. 1151 - 1160
[3] Carbohydrate Research, 1980, vol. 78, p. 195 - 204
[4] Journal of the American Chemical Society, 1990, vol. 112, # 20, p. 7373 - 7381
[5] American Chemical Journal, 1903, vol. 29, p. 496[6] American Chemical Journal, 1904, vol. 31, p. 596
[7] Chemistry of Heterocyclic Compounds (New York, NY, United States), 1991, vol. 27, # 4, p. 407 - 409[8] Khimiya Geterotsiklicheskikh Soedinenii, 1991, # 4, p. 512 - 515
[9] Chemical Research in Toxicology, 1998, vol. 11, # 9, p. 1082 - 1088
[10] Journal of the Chemical Society, 1956, p. 2388,2392[11] Journal of the Chemical Society, 1958, p. 3028,3032
[12] Bioorganic and Medicinal Chemistry, 2002, vol. 10, # 8, p. 2671 - 2680
[13] Journal of Pharmacology and Experimental Therapeutics, 2007, vol. 322, # 3, p. 1023 - 1035
[14] Journal of Chemical Research, 2007, # 5, p. 281 - 283
[15] Patent: WO2010/82128, 2010, A1, . Location in patent: Page/Page column 18
[16] Patent: US2011/282046, 2011, A1, . Location in patent: Page/Page column 8
[17] Croatica Chemica Acta, 2017, vol. 90, # 4, p. 625 - 636
24
[ 3650-93-9 ]
[ 23945-44-0 ]
[ 71-30-7 ]
Reference：
[1] Chemical Research in Toxicology, 1996, vol. 9, # 4, p. 745 - 750
25
[ 71-30-7 ]
[ 98-88-4 ]
[ 26661-13-2 ]
Yield
Reaction Conditions
Operation in experiment
40 kg
With dmap; triethylamine In acetonitrile at 5 - 45℃; for 3 h; Inert atmosphere; Large scale
Reactor after the replacement of nitrogen, adding 100L acetonitrile, 22 kg (196mol) no water cytosine, 25gDMAP, 24 kg triethylamine, in 5-8 °C lower, slowly dropping 34 kg benzoyl chloride, after dripping, natural to room temperature, in the 25 °C stirring for one hour, then slowly heated to 40-45 °C insulation two hours, then cooling down to room temperature, filter press, the filtrate collected after acetonitrile 60L recycling, the filter cake with water and ethanol washing, drying to obtain the kind of white solid 40 kg, liquid phase content is 99.2percent.
Reference：
[1] Patent: US2011/245458, 2011, A1,
[2] Chemical Communications, 2017, vol. 53, # 64, p. 8952 - 8955
[3] Heterocyclic Communications, 2007, vol. 13, # 4, p. 251 - 256
[4] Russian Journal of Organic Chemistry, 2008, vol. 44, # 3, p. 358 - 361
[5] Journal of the Chemical Society, 1956, p. 2388,2392[6] Journal of the Chemical Society, 1958, p. 3028,3032
[7] Chemistry of Natural Compounds, 1983, vol. 19, # 5, p. 580 - 582[8] Khimiya Prirodnykh Soedinenii, 1983, # 5, p. 617 - 619
[9] Patent: US6075143, 2000, A,
[10] Chemistry - A European Journal, 2011, vol. 17, # 51, p. 14508 - 14517
[11] Patent: CN105541728, 2016, A, . Location in patent: Paragraph 0023; 0024
26
[ 71-30-7 ]
[ 93-97-0 ]
[ 26661-13-2 ]
Yield
Reaction Conditions
Operation in experiment
41 kg
With dmap; triethylamine In acetonitrile at 5 - 50℃; for 3 h; Inert atmosphere; Large scale
Reactor after the replacement of nitrogen, adding 200L acetonitrile, 22 kg (196mol) no water cytosine, 50gDMAP, 28 kg triethylamine, in 5-10 °C lower, slowly dropping 96 kg (benzoic anhydride solution: 50 wt percent) acetonitrile solution of benzoic anhydride, after dripping, natural to room temperature, in the 25 °C stirring for one hour, then slowly heated to 45-50 °C thermal insulation 2 hours, then reduced to room temperature, filter press, the filtrate collected after acetonitrile 132L recycling, the filter cake is washed with water and ethanol, dried to obtain a white solid 41 kg, liquid phase content of 99.14percent.
Reference：
[1] Collection of Czechoslovak Chemical Communications, 1989, vol. 54, # 8, p. 2190 - 2210
[2] Patent: CN105541728, 2016, A, . Location in patent: Paragraph 0027; 0028
27
[ 123413-57-0 ]
[ 26661-13-2 ]
[ 71-30-7 ]
Reference：
[1] Chemical and Pharmaceutical Bulletin, 1989, vol. 37, # 9, p. 2547 - 2549
28
[ 77287-34-4 ]
[ 51953-18-5 ]
[ 156-81-0 ]
[ 120-89-8 ]
[ 108-53-2 ]
[ 71-30-7 ]
[ 144-62-7 ]
[ 113-00-8 ]
[ 127-17-3 ]
[ 66-22-8 ]
[ 56-06-4 ]
[ 66224-66-6 ]
[ 57-13-6 ]
[ 56-40-6 ]
Yield
Reaction Conditions
Operation in experiment
1.6 mg
With copper(II) choride dihydrate In water at 80℃; for 24 h;
General procedure: To model the chemical environment on the outer side of thetubular structures, NH2CHO (200 μL) was mixed with thesodium silicate solution (2.0 mL) in the presence of preformedMSH [ZnCl2, FeCl2·4H2O, CuCl2·2H2O, Fe2(SO4)3·9H2O,and MgSO4] (2.0percent w/w) at 80 °C for 24 h. In two selectedcases [FeCl2 and Fe2(SO4)3·9H2O], NH2CHO (200 μL) wasmixed with the sodium silicate solution (2.0 mL) in the presence of selected growing MSH (starting from 2.0percent w/w ofthe corresponding salt’s pellet) at 80 °C for 24 h. For the innerenvironment, NH2CHO (200 μL) was mixed with distilledwater (2.0 mL) in the presence of selected MSH (2.0percent w/w) at80 °C for 24 h. The reaction of NH2CHO (10percent v/v) with thesodium silicate solution (pH 12) without MSH membranes wasalso analyzed under similar experimental conditions. Theproducts were analyzed by gas chromatography associatedwith mass spectrometry (GC-MS) after treatment with N,Nbis-trimethylsilyl trifluoroacetamide in pyridine (620 μL) at 60°C for 4 h in the presence of betulinol (CAS Registry Number473-98-3) as the internal standard (0.2 mg). Mass spectrometrywas performed by the following program: injection temperature280 °C, detector temperature 280 °C, gradient 100 °C for 2min, and 10 °C/min for 60 min. To identify the structure of theproducts, two strategies were followed. First, the spectra werecompared with commercially available electron mass spectrumlibraries such as NIST (Fison, Manchester, U.K.). Second, GCMSanalysis was repeated with standard compounds. Allproducts have been recognized with a similarity index (SI)greater than 98percent compared to that of the reference standards.The analysis was limited to products of ≥1 ng/mL, and theyield was calculated as micrograms of product per startingformamide. For further experimental details, see the SupportingInformation.
Reference：
[1] Chemical and Pharmaceutical Bulletin, 1980, vol. 28, # 3, p. 932 - 938
32
[ 71-30-7 ]
[ 19263-02-6 ]
[ 55662-66-3 ]
Reference：
[1] Journal of Organic Chemistry, 1984, vol. 49, # 21, p. 4021 - 4025
33
[ 71-30-7 ]
[ 3018-12-0 ]
[ 506-77-4 ]
Reference：
[1] Environmental Science and Technology, 2000, vol. 34, # 9, p. 1721 - 1728
34
[ 77287-34-4 ]
[ 156-81-0 ]
[ 849585-22-4 ]
[ 617-48-1 ]
[ 2491-15-8 ]
[ 110-15-6 ]
[ 108-53-2 ]
[ 71-30-7 ]
[ 113-00-8 ]
[ 127-17-3 ]
[ 66-22-8 ]
[ 66224-66-6 ]
[ 56-40-6 ]
[ 302-72-7 ]
[ 18514-52-8 ]
Yield
Reaction Conditions
Operation in experiment
0.18 mg
With ferric sulfate nonahydrate In water at 80℃; for 24 h;
General procedure: To model the chemical environment on the outer side of thetubular structures, NH2CHO (200 μL) was mixed with thesodium silicate solution (2.0 mL) in the presence of preformedMSH [ZnCl2, FeCl2·4H2O, CuCl2·2H2O, Fe2(SO4)3·9H2O,and MgSO4] (2.0percent w/w) at 80 °C for 24 h. In two selectedcases [FeCl2 and Fe2(SO4)3·9H2O], NH2CHO (200 μL) wasmixed with the sodium silicate solution (2.0 mL) in the presence of selected growing MSH (starting from 2.0percent w/w ofthe corresponding salt’s pellet) at 80 °C for 24 h. For the innerenvironment, NH2CHO (200 μL) was mixed with distilledwater (2.0 mL) in the presence of selected MSH (2.0percent w/w) at80 °C for 24 h. The reaction of NH2CHO (10percent v/v) with thesodium silicate solution (pH 12) without MSH membranes wasalso analyzed under similar experimental conditions. Theproducts were analyzed by gas chromatography associatedwith mass spectrometry (GC-MS) after treatment with N,Nbis-trimethylsilyl trifluoroacetamide in pyridine (620 μL) at 60°C for 4 h in the presence of betulinol (CAS Registry Number473-98-3) as the internal standard (0.2 mg). Mass spectrometrywas performed by the following program: injection temperature280 °C, detector temperature 280 °C, gradient 100 °C for 2min, and 10 °C/min for 60 min. To identify the structure of theproducts, two strategies were followed. First, the spectra werecompared with commercially available electron mass spectrumlibraries such as NIST (Fison, Manchester, U.K.). Second, GCMSanalysis was repeated with standard compounds. Allproducts have been recognized with a similarity index (SI)greater than 98percent compared to that of the reference standards.The analysis was limited to products of ≥1 ng/mL, and theyield was calculated as micrograms of product per startingformamide. For further experimental details, see the SupportingInformation.
General procedure: To model the chemical environment on the outer side of thetubular structures, NH2CHO (200 μL) was mixed with thesodium silicate solution (2.0 mL) in the presence of preformedMSH [ZnCl2, FeCl2·4H2O, CuCl2·2H2O, Fe2(SO4)3·9H2O,and MgSO4] (2.0percent w/w) at 80 °C for 24 h. In two selectedcases [FeCl2 and Fe2(SO4)3·9H2O], NH2CHO (200 μL) wasmixed with the sodium silicate solution (2.0 mL) in the presence of selected growing MSH (starting from 2.0percent w/w ofthe corresponding salt’s pellet) at 80 °C for 24 h. For the innerenvironment, NH2CHO (200 μL) was mixed with distilledwater (2.0 mL) in the presence of selected MSH (2.0percent w/w) at80 °C for 24 h. The reaction of NH2CHO (10percent v/v) with thesodium silicate solution (pH 12) without MSH membranes wasalso analyzed under similar experimental conditions. Theproducts were analyzed by gas chromatography associatedwith mass spectrometry (GC-MS) after treatment with N,Nbis-trimethylsilyl trifluoroacetamide in pyridine (620 μL) at 60°C for 4 h in the presence of betulinol (CAS Registry Number473-98-3) as the internal standard (0.2 mg). Mass spectrometrywas performed by the following program: injection temperature280 °C, detector temperature 280 °C, gradient 100 °C for 2min, and 10 °C/min for 60 min. To identify the structure of theproducts, two strategies were followed. First, the spectra werecompared with commercially available electron mass spectrumlibraries such as NIST (Fison, Manchester, U.K.). Second, GCMSanalysis was repeated with standard compounds. Allproducts have been recognized with a similarity index (SI)greater than 98percent compared to that of the reference standards.The analysis was limited to products of ≥1 ng/mL, and theyield was calculated as micrograms of product per startingformamide. For further experimental details, see the SupportingInformation.
Sodium isopropoxide (61.6 g, 0.75 mol) was mixed with 270 mL of isopropanol Into the reactor and stir well;Followed by input 3-hydroxyacrylonitrile sodium salt(27.3 g,0.3 mol) and O-Methylisourea monomethyl sulfate (67.0 g, 0.36 mol);70 C and cyclization reaction for 8 hours to obtain a cyclization reaction solution; at atmospheric pressure to evaporate isopropyl alcohol, To give the intermediate; and further adding 100 mL of concentrated hydrochloric acid to the intermediate, raising the temperature to 100 C Incubate for 1 hour; heat and then add 60mL of water to the solution for hot filtration, the resulting filtrate cooled to room temperature; The filtrate was added with 10mol / L sodium hydroxide solution to adjust the pH value. When the pH was 7 ~ 7.5, it was cooled to 10 70 C. After cooling, the mixture was filtered, washed and dried to obtain cytosine 30.4g,The yield was 91.2% and the HPLC content was 99.2%.
With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 15℃; for 1h;Sonication;
The cytosine (55.6g, 0.5mol), N-bromosuccinimide (106.8g, 0 . 6mol) and DMF150mL in added in the reaction bottle, cooling to 15 C ultrasonic reaction 1h, TLC raw material the reaction is complete, filtering, the filter cake is washed with water (20 ml × 2) washing, drying to obtain 5-bromocytosine (90.9g, 95.6%).
93.6%
With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 25℃; for 10h;Large scale;
To a solution of cytosine (300 g, 2.70 mol, 1.00 equiv) in DMF (1.5 L) was added NBS (480 g, 2.70 mol, 1.00 equiv). The mixture was stirred at 25 C for 10 h at which time the crude 1H NMR spectrum indicated that the reaction was complete. The reaction mixture was filtered and the filter cake was washed with water (1 L x 4). The solid was collected and dried under reduced pressure to afford 5-bromocytosine (480 g, 2.53 mol, 93.6% yield) as a white solid. 1H NMR (400MHz, DMSO-d6) d 10.80 (br s, 1H), 11.36 - 10.16 (m, 1H), 7.74 (s, 1H), 6.83 (br s, 2H).
84.8%
With bromine; acetic acid; at 70℃; for 8h;
To a solution of 4-aminopyrimidin-2(1H)-one (2 g, 18 mmol) inacetic acid (10 mL) was added bromine (3.6 g, 22.5 mmol). The reactionmixture was stirred at 70 C for 8 h. The reaction mixture was dilutedwith H2O (30 mL) and the light yellow precipitate was filtered andwashed with water. The solid was then dried under reduced pressure togive the title compound (2.91 g, 84.8% yield). 1H NMR (300 MHz,DMSO-d6) delta 10.86 (s, 1H), 7.75 (s, 1H), 6.85 (s, 1H).
Example 2; A mixture of cytosine (2.0 g, 18.0 mmol), ammonium sulfate (0.24 g, 1.82 mmol), and hexamethyldisilazane (16.13 g, 100 mmol) was heated to reflux for 45 minutes until a clear solution was obtained. Some gas evolved (ammonia). The reaction mixture was cooled to 52C and concentrated in the vacuum whereby a colourless solid precipitated. 26.4 g of dichloromethane, lithium trifluoromethane sulfonate (2.53 g, 16.2 mmol) and the "chloro sugar" C-137 (6.96 g, 16.2 mmol) were added. The slightly beige mixture was stirred for 2 hours at ambient temperature (20-25C), products (anomeric mixture [(beta-isomer) : (alpha-isomer) 59.5:40.1]) : starting material 99.1 : 0.9. Then the solvent was removed at 38C. A brownish solid was obtained. The solid was dissolved in 6.0 g ethyl acetate. The solution was added drop wise to a mixture of 11 g of aqueous sodium hydrogen carbonate (5 weight% solution in water), 11.0g of water, 17.4 g of ethyl acetate, 3.6 g of cyclohexane and 7.0 g of acetonitrile at 32C. The obtained reaction mixture was stirred over night at ambient temperature, and then for 3 hours at 0C. The precipitate of the blocked (protected) nucleoside was filtered off, washed with 6.0 g of water, and finally with 7.0 g of a mixture of acetonitrile and ethyl acetate (1:1). Yield: 3.63 g; 40.1%.
With ferric sulfate nonahydrate; In water; at 80℃; for 24h;pH 7.57;
General procedure: To model the chemical environment on the outer side of thetubular structures, NH2CHO (200 muL) was mixed with thesodium silicate solution (2.0 mL) in the presence of preformedMSH [ZnCl2, FeCl2·4H2O, CuCl2·2H2O, Fe2(SO4)3·9H2O,and MgSO4] (2.0% w/w) at 80 C for 24 h. In two selectedcases [FeCl2 and Fe2(SO4)3·9H2O], NH2CHO (200 muL) wasmixed with the sodium silicate solution (2.0 mL) in the presence of selected growing MSH (starting from 2.0% w/w ofthe corresponding salt?s pellet) at 80 C for 24 h. For the innerenvironment, NH2CHO (200 muL) was mixed with distilledwater (2.0 mL) in the presence of selected MSH (2.0% w/w) at80 C for 24 h. The reaction of NH2CHO (10% v/v) with thesodium silicate solution (pH 12) without MSH membranes wasalso analyzed under similar experimental conditions. Theproducts were analyzed by gas chromatography associatedwith mass spectrometry (GC-MS) after treatment with N,Nbis-trimethylsilyl trifluoroacetamide in pyridine (620 muL) at 60C for 4 h in the presence of betulinol (CAS Registry Number473-98-3) as the internal standard (0.2 mg). Mass spectrometrywas performed by the following program: injection temperature280 C, detector temperature 280 C, gradient 100 C for 2min, and 10 C/min for 60 min. To identify the structure of theproducts, two strategies were followed. First, the spectra werecompared with commercially available electron mass spectrumlibraries such as NIST (Fison, Manchester, U.K.). Second, GCMSanalysis was repeated with standard compounds. Allproducts have been recognized with a similarity index (SI)greater than 98% compared to that of the reference standards.The analysis was limited to products of ?1 ng/mL, and theyield was calculated as micrograms of product per startingformamide. For further experimental details, see the SupportingInformation.
With magnesium sulfate; In water; at 80℃; for 24h;pH 7.57;
General procedure: To model the chemical environment on the outer side of thetubular structures, NH2CHO (200 muL) was mixed with thesodium silicate solution (2.0 mL) in the presence of preformedMSH [ZnCl2, FeCl2·4H2O, CuCl2·2H2O, Fe2(SO4)3·9H2O,and MgSO4] (2.0% w/w) at 80 C for 24 h. In two selectedcases [FeCl2 and Fe2(SO4)3·9H2O], NH2CHO (200 muL) wasmixed with the sodium silicate solution (2.0 mL) in the presence of selected growing MSH (starting from 2.0% w/w ofthe corresponding salt?s pellet) at 80 C for 24 h. For the innerenvironment, NH2CHO (200 muL) was mixed with distilledwater (2.0 mL) in the presence of selected MSH (2.0% w/w) at80 C for 24 h. The reaction of NH2CHO (10% v/v) with thesodium silicate solution (pH 12) without MSH membranes wasalso analyzed under similar experimental conditions. Theproducts were analyzed by gas chromatography associatedwith mass spectrometry (GC-MS) after treatment with N,Nbis-trimethylsilyl trifluoroacetamide in pyridine (620 muL) at 60C for 4 h in the presence of betulinol (CAS Registry Number473-98-3) as the internal standard (0.2 mg). Mass spectrometrywas performed by the following program: injection temperature280 C, detector temperature 280 C, gradient 100 C for 2min, and 10 C/min for 60 min. To identify the structure of theproducts, two strategies were followed. First, the spectra werecompared with commercially available electron mass spectrumlibraries such as NIST (Fison, Manchester, U.K.). Second, GCMSanalysis was repeated with standard compounds. Allproducts have been recognized with a similarity index (SI)greater than 98% compared to that of the reference standards.The analysis was limited to products of ?1 ng/mL, and theyield was calculated as micrograms of product per startingformamide. For further experimental details, see the SupportingInformation.
(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (2R,5R)-5-(4-amino-2-oxo-1,2-dihydro-1-pyrimidinyl)-1,3-oxathiolane-2-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
78%
(1) (3 g) was added to dry DMF (1.0 ml) and dichloromethane (40 ml) in a reaction flask A, and cooled to about 5 C with stirring.Add a solution of thionyl chloride in dichloromethane (1.0 ml + 10 ml).After the dropwise addition, continue to stir at 18-24 C for about 10 h.Concentrate under reduced pressure at 40 C until no liquid dripping, and cool to room temperature to obtain a chloride. In another reaction vial B, cytosine (1.2 g) was added,Methanesulfonic acid (0.1 ml) of hexamethyldisilazane (5 ml) and toluene (10 ml) were heated under reflux for 3 h to give a clear solution.Tetrabutylammonium bromide (3.35 g) was added, and the chlorination liquid obtained in the above reaction flask A was added dropwise under a gentle reflux condition, and the dropping funnel was washed with dichloromethane (2 ml), and the resulting mixture was heated under reflux for 4 h. ,Cool to room temperature, add 30% potassium hydroxide 10 ml solution, stir the suspension for 2 h, add n-hexane (20 ml) at room temperature, stir for 6 hours, filter, wash the solid with 60-90 C petroleum ether,Drying white solid (2) (3.09 g, 78%), purity: 98.8%
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
Life Science
For Research Only
88K+ Compounds
Competitive Price
1-2 Day Shipping
