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Initiator microwave reactor

Manufactured by Biotage
Sourced in Sweden

The Initiator+ microwave reactor is a laboratory instrument designed for rapid and efficient chemical synthesis. It utilizes microwave technology to provide precise temperature and pressure control, enabling the acceleration of chemical reactions. The Initiator+ is capable of performing a wide range of synthesis procedures, making it a versatile tool for researchers and chemists in various fields.

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9 protocols using initiator microwave reactor

1

Glycation of Model Protein Myoglobin

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The glycation products used in this study were generated as described earlier using either conventional glycation in solution (ACG) or reaction under dry conditions (MWG) [23 (link)]. Briefly, the MiliQ water solution mixtures of a model protein MB and melibiose (mel) in a 1:100 molar ratio (protein:carbohydrate) were prepared, followed by the ACG or MWG reaction. In the ACG method, the MB/mel solution was incubated for 21 days at room temperature, while in the MWG method, an analogous MB/mel solution was lyophilized and incubated in a microwave initiator reactor (Biotage, Uppsala, Sweden) for 45 min at 85 °C. Next, the samples were dissolved in MilliQ water and centrifuged at 5000× g for 15 min to remove any insoluble precipitates. The obtained supernatants were dialyzed against MilliQ water on Amicon Ultra-15 centrifuge filters (Merck Millipore, Burlington, MA, USA) with a 30 kDa cut-off to separate unreacted substrates and MB monomers. The resulting glycation products were lyophilized and stored at −20 °C for further characterization.
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2

Synthesis of Pyrimidine-Pyrazole Compound 69

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Example 69

[Figure (not displayed)]

A 5 mL microwave mixture vessel equipped with a stir bar was charged with 4-chloro-6-(2-(4-fluorophenyl)pyrrolidin-1-yl)pyrimidine compound 6 (0.100 mg, 0.360 mmol), 5-(pyridin-3-yl)-1H-pyrazol-3-amine (63.44 mg, 0.396 mmol) and HCl in 1,4-dioxane (4.00 M, 0.10 mL, 0.396 mmol) in N-methylpyrrolidone (3 mL). The mixture was heated to 200° C. for 30 minutes in a Biotage Microwave Initiator reactor, then cooled to ambient temperature. The mixture was slowly added to half-saturated NaHCO3 solution in water (˜50 mL). Precipitation of solid was observed. The solid was then filtered off and dried. The resulting crude solid was then purified by flash column chromatography on silica gel using 0-5% MeOH in DCM (v/v) as eluent to obtain compound 69 as brown solids (20 mg, 14%). 1H NMR (400 MHz, DMSO-d6) δ 12.84 (br, 1H), 9.29 (br, 1H), 8.93 (br, 1H), 8.93 (br, 1H), 8.08 (br, 2H), 7.47 (br, 1H), 7.10 (m, 4H), 6.63 (br, 1H), 5.04 (br, 1H), 3.74 (m, 2H), 2.33 (m, 1H), 1.95-1.75 (m, 3H); ESI-MS: calcd for (C22H20FN7) 401, found 402 (MH+).

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3

Synthesis of Pyrimidine-Pyrazole Heterocycle

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Example 70

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A 5 mL microwave mixture vessel equipped with a stir bar was charged with 4-chloro-6-(2-(4-fluorophenyl)pyrrolidin-1-yl)pyrimidine compound 6 (0.200 mg, 0.720 mmol), 5-(pyridin-4-yl)-1H-pyrazol-3-amine (126.89 mg, 0.792 mmol) and HCl in 1,4-dioxane (4.00 M, 0.19 mL, 0.792 mmol) in N-methylpyrrolidone (3.5 mL). The mixture was heated to 200° C. for 30 minutes in a Biotage Microwave Initiator reactor, then cooled to ambient temperature. The mixture was slowly added to half-saturated NaHCO3 solution in water (˜50 mL). Precipitation of solid was observed. The solid was then filtered off and dried. The resulting crude solid was then purified by flash column chromatography on silica gel using 0-5% MeOH in DCM (v/v) as eluent to obtain compound 70 as orange solids (38 mg, 13%). 1H NMR (400 MHz, DMSO-d6) δ 13.02 (br, 1H), 9.34 (br, 1H), 8.61 (br, 2H), 8.08 (br, 1H), 7.67 (s, 2H), 7.20 (m, 4H), 6.76 (br, 1H), 6.35 (br, 1H), 5.02 (br, 1H), 3.74 (m, 2H), 2.33 (m, 1H), 1.95-1.75 (m, 3H); ESI-MS: calcd for (C22H20FN7) 401, found 402 (MH+).

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4

Synthesis of 1,2,3-Triazole-Linked Pyrimidine Derivative

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N-(4-(1H-1,2,3-Triazol-1-yl)benzyl)-2-chloro-5-methylpyrimidin-4-amine (0.19
g, 0.63 mmol) was combined with (2-isopropylphenyl)boronic acid (0.31
g, 1.90 mmol), sodium carbonate (2.0 M in water, 1.23 mL, 2.53 mmol),
and DPP-Pd Silicycle 0.26 mmol/g (0.30 g) in DMF (4.50 mL). The reaction
was sealed and heated at 150 °C for 30 min in a Biotage Initiator
microwave reactor. The resulting mixture was filtered over Celite
and purified by HPLC (gradient 20–100% acetonitrile w/0.1%
TFA in water w/0.1% TFA) to give, after lyophilization, N-(4-(1H-1,2,3-triazol-1-yl)benzyl)-5-methyl-2-(2-isopropylphenyl)-pyrimidin-4-amine
(70) as a TFA salt (0.01 g, 0.02 mmol, 30%). 1H NMR (400 MHz, CDCl3) δ 8.82 (dd, J = 3.4, and 7.9 Hz, 1 H), 8.02–7.93 (m, 2 H), 7.76 (d, J = 1.4 Hz, 1 H), 7.64–7.56 (m, 2 H), 7.51–7.33
(m, 5 H), 7.25–7.17 (m, 1 H), 4.88 (d, J =
5.9 Hz, 2 H), 3.19 (p, J = 6.8 Hz, 1H), 2.22 (s,
3 H), 1.10 (d, J = 1.2 Hz, 3 H) and 1.09–1.07
(m, 3 H). 13C NMR (100 MHz, CDCl3) δ 162.02,
160.18, 148.00, 140.63, 138.03, 136.14, 134.35, 134.28, 131.89, 130.34,
129.25, 129.00, 126.61, 126.04, 122.04, 121.99, 120.74, 113.81, 44.62,
29.43, 23.95, 13.71 and 13.67. LC-MS retention time (method 1) = 2.938
min and (method 2) = 1.756 min. HRMS: (ESI) m/z (M + H)+ (calculated for C23H25N6 385.2135) found, 385.2146.
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5

Anhydrous Ether Schlenk Synthesis

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Reactions requiring an argon atmosphere were carried out using standard Schlenk techniques in a fume hood. Anhydrous diethyl ether was obtained from a dry solvent system and stored over 4 Å molecular sieves. All commercial materials were used as received without further purification. Microwave reactions were performed using a Biotage Initiator microwave reactor. Column chromatography was performed using a Biotage Isolera flash chromatography system. High-resolution mass spectra were collected on a JEOL AccuTOF 4G LC-plus equipped with an ionSense DART source. NMR spectra were recorded on a 500 MHz JEOL ECZ spectrometer. Chemical shifts δ are reported in ppm downfield from tetramethylsilane by referencing the spectra to residual solvent signals.
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6

Ruthenium-Catalyzed tert-Butyl Acrylate Polymerization

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A typical example of RuAAC polymerization of tBuAH is described below.
tBuAH (1.00 g, 4.79 mmol) was dissolved in DMF (5.0 mL) at room temperature under a nitrogen atmosphere. Then, Cp*RuCl(PPh3)2 (421 mg, 0.529 mmol) was added to the reaction solution. The reaction solution was stirred at 50 °C for 8 h using a Biotage Initiator+ microwave reactor (Uppsala, Sweden) (2.45 GHz, the high adsorption level). The reaction solution was diluted with ethyl acetate (5.0 mL) and added dropwise to hexane (50 mL). The suspension was centrifuged at 4000 rpm for 10 min to recover the product as a precipitate. After drying under reduced pressure, the product was obtained as a brown solid (367 mg, 36.7%).
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7

4-Chloro-2-Substituted 1H-Imidazo[4,5-c]Quinoline Synthesis

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The appropriate 4-chloro-2-substituted 1H-imidazo[4,5-c]quinoline (46b,h,o,t) starting material (0.05 mmol, 1 equiv) and the appropriate halogenated aniline compound (47a–c) (0.15–0.25 mmol, 3–5 equiv) were added to 1 mL of ethanol in a 2 to 5 mL microwaveable vial. The reaction contents were degassed with N2(g) for 15 min, and the reaction was set up in an Initiator microwave reactor (Biotage, Charlotte, NC) at 130 °C for 6 h. The reaction mixture was filtered through a silica plug. The filtrate was evaporated in vacuo, and the product was purified by flash chromatography with a 15% ethyl acetate in hexane eluent system.
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8

Microwave-Assisted Synthesis of NH4CN Polymers

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The NH4CN polymers synthesized in this work were obtained following the methodology detailed in [10 (link),37 (link)] using a Biotage Initiator+ microwave reactor purchased from Biotage (Uppsala, Sweden). The initial equimolar concentrations of NaCN and NH4Cl were always 1 M. The synthesis of the control polymers prepared at 80 °C is described in [29 (link)]. All syntheses were carried out in triplicate. The details about the reaction time and temperature for each reaction and the conversion values reached for each case are described in Table S1. All the corresponding average values of conversion, α (%), are shown as green lines in Figure 1.
All security and safety measures were taken during the development of the experiments, considering the safety information provided by the Sigma-Aldrich supplier (St. Louis, MO, United States) about NaCN and NH4Cl. On the other hand, although HCN-derived polymers have been shown as biocompatible [19 (link),20 (link),21 (link),22 (link),23 (link),24 (link)], the cyanide polymers synthesized in the present work were handled with the same security measures as NaCN.
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9

Epoxy Resin Synthesis via Microwave

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To the microwave reaction vial, 20 g of Epidian 6 and 5% mass TBAB were introduced. The whole mixture was placed in a Biotage® (Uppsala, Sweden) Initiator+ microwave reactor and stirred by heating the system to 105 °C to obtain a homogeneous mixture. The reactor operates with a maximum power of 400 W from a magnetron at 2.45 GHz, and the appropriate amount of energy supplied was automatically controlled using the deflector (shutter) present in the reactor in order to maintain the set reaction temperature of 105 °C. CO2 (75 mL/min) was continuously introduced through a Teflon capillary. The reaction was carried out for 44 h and its progress was monitored using FT-IR spectroscopy. The product obtained was a white solid.
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