* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With carbazic acid In neat (no solvent) at 100℃; for 5 h; Green chemistry
7.6 g (100.0 mmol) of solid hydrazine (H3N + NHCO2-) and adipic acid (7.3 g, 50.0 mmol) were mixed in a mortar without a solvent for 10 minutes and stirred at 100 ° C for 5 hours. To confirm the structure and composition of the product produced in this process and analyzed using 400 MHz NMR (nuclear magnetic resonance) and elemental analysis) .As a result of the analysis, the product was adipohydrazide (C6H14N4O2), the conversion rate was 96percent or more, and the yield was 95percent or more. Yield (8.27 g, 96percent or more);
Reference:
[1] Patent: KR2015/88523, 2015, A, . Location in patent: Paragraph 0127-0130
[2] Patent: US2016/31858, 2016, A1,
2
[ 124-04-9 ]
[ 10195-79-6 ]
[ 1071-93-8 ]
Yield
Reaction Conditions
Operation in experiment
96%
at 100℃; for 5 h;
5.4 g (50.0 mmol) of anhydrous hydrazinium hydrazinecarboxylate and 7.3 g (50.0 mmol) of adipic acid were mixed in a mortar without a solvent for 10 minutes and stirred at 100 ° C for 5 hours.In order to confirm the structure and composition of the product formed in this process, 400 MHz NMR (Nuclear Magnetic Resonance) and elemental analysis were used.
Reference:
[1] Angewandte Chemie - International Edition, 2012, vol. 51, # 8, p. 1835 - 1839
[2] Journal of the American Chemical Society, 2014, vol. 136, # 5, p. 1698 - 1701
[3] Journal of the American Chemical Society, 2015, vol. 137, # 10, p. 3494 - 3497
[4] Chemical Communications, 2015, vol. 51, # 70, p. 13470 - 13473
4
[ 67-56-1 ]
[ 124-04-9 ]
[ 868-72-4 ]
Yield
Reaction Conditions
Operation in experiment
253 g
Stage #1: at 80℃; Stage #2: at 80℃;
Thionyl chloride (323 g, 2.71 mol) was added in 70 ml portions over 2 h to adipic acid (197 g, 1.35 mol) heated at 80 °C in a three-neck round bottom flask equipped with a reflux condenser and a constant pressure dropping funnel. The mixture was stirred until gas evolution ceased and partial solid adipic acid still remained. An additional 100 ml of thionyl chloride was added in 7 h, and heating was continued until gas evolution ceased. Bromine (473 g, 2.96 mol) was added dropwise to the pale yellow reaction mixture over an ice bath, and a white precipitate formed during the addition. The white precipitate was collected by filtration and recrystallized from MeOH to offer 253 g of 3 as white power with a yield of 53percent.1H NMR (400 MHz, CDCl3, δ ppm): 2.00~2.05 (m, 2H), 2.28~2.35 (m, 2H), 3.80 (s, 6H), 4.24~4.26 (t, 2H).
Reference:
[1] Chemistry - A European Journal, 2012, vol. 18, # 4, p. 1127 - 1141
[2] Journal of Organic Chemistry, 1972, vol. 37, p. 2418 - 2423
[3] Synthesis (Germany), 2012, vol. 44, # 11, p. 1736 - 1744
[4] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 21, p. 5855 - 5859
5
[ 124-04-9 ]
[ 868-72-4 ]
Reference:
[1] Tetrahedron Asymmetry, 2003, vol. 14, # 1, p. 127 - 137
[2] Journal of the American Chemical Society, 2011, vol. 133, # 46, p. 18992 - 18998
[3] Journal of the American Chemical Society, 2016, vol. 138, # 6, p. 2014 - 2020
6
[ 124-04-9 ]
[ 869-10-3 ]
Reference:
[1] Chemische Berichte, 1902, vol. 35, p. 2067
7
[ 124-04-9 ]
[ 64-17-5 ]
[ 869-10-3 ]
Reference:
[1] Bulletin des Societes Chimiques Belges, 1968, vol. 77, p. 579 - 585
8
[ 124-04-9 ]
[ 25561-30-2 ]
[ 354-38-1 ]
[ 18105-31-2 ]
[ 55982-15-5 ]
Reference:
[1] Environmental Science and Technology, 1998, vol. 32, # 16, p. 2357 - 2370
Reference:
[1] Journal of applied chemistry of the USSR, 1984, vol. 57, # 10 pt 2, p. 2138 - 2142
14
[ 124-04-9 ]
[ 75-65-0 ]
[ 52221-07-5 ]
Reference:
[1] Chemistry and Physics of Lipids, 2002, vol. 119, # 1-2, p. 51 - 68
[2] Chemical Communications, 1999, # 9, p. 823 - 824
15
[ 124-04-9 ]
[ 104-76-7 ]
[ 103-23-1 ]
Reference:
[1] Asian Journal of Chemistry, 2014, vol. 26, # 17, p. 5769 - 5772
[2] Kobunshi Kagaku, 1945, vol. 2, p. 287,296[3] Chem.Abstr., 1950, p. 5144
16
[ 108-94-1 ]
[ 124-04-9 ]
[ 693-23-2 ]
[ 50905-10-7 ]
[ 142-62-1 ]
Reference:
[1] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1986, vol. 35, # 1, p. 72 - 75[2] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1986, # 1, p. 85 - 88
17
[ 2408-01-7 ]
[ 124-04-9 ]
[ 1577-22-6 ]
[ 693-23-2 ]
[ 33053-07-5 ]
[ 50905-10-7 ]
[ 142-62-1 ]
Reference:
[1] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1983, vol. 32, # 3, p. 543 - 545[2] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1983, # 3, p. 603 - 606
18
[ 108-94-1 ]
[ 502-44-3 ]
[ 124-04-9 ]
[ 693-23-2 ]
[ 50905-10-7 ]
[ 32673-76-0 ]
[ 142-62-1 ]
Reference:
[1] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1986, vol. 35, # 1, p. 72 - 75[2] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1986, # 1, p. 85 - 88
With carbonic acid dimethyl ester; at 180℃; under 10343.2 Torr; for 5h;Inert atmosphere;
Figure 3 presents a series of methyl esterification reactions using various kinds ofcarboxylic acids with diroethyicarbonate in methanol. Each reaction used 20 g. carboxylic acid, 5 molar equivalents of dimethylcarbonate (DMC (2.5 equivalents for levulinic acid), 300 g. of absolute methanol, at. 1 8<fC. 5h, 200 psi >. All acids, except levulinic acid, completely converted in the 20 reaction. Each exh ibited high selectivity (e.g., 40%) of the fully esters iied target (d lesser) species. Figures 3A and 38 represent ester; fication of succinic acid and malic acid, respectively, which produced about a yield of about 60% and 79%, respectively, oft.be corresponding di-esters. in Figure 3C, about 71 % of levulinic acid was consumed in the reaction to produce about 70% yield of the ester. The esterification reaction with adipie acid produced a mixed product of the corresponding 25 mono-ester and di-ester, respectively, at about 60% and 40 yield.
With sulfonated poly-divinylbenzene-co-triallylamine; at 24.84℃; for 10h;
General procedure: For the synthesis of biodiesel compounds 1 mmol of each of the long chain fatty acids were taken in 5 mL of methanol. 10 mg PDVTA-SO3H was added to the reaction mixtures under stirring condition and the esterification was allowed to proceed at room temperature. The progress of the reaction was monitored by TLC. After completion of the reaction, the catalyst was filtered off and the solvent was removed in a rotary evaporator to get the desired product. The solid compounds were characterized by 1H and 13C NMR spectroscopy. The separated catalyst was washed several times with methanol, dried in vacuum and reused further to check its recycling efficiency.
109.6 g
With hydrogenchloride; In water; toluene; at 25 - 85℃; for 8.75h;
Conc.HC1 (8.6 ml) was added to a mixture of adipic acid compound of formula-22 (100 gm) and methanol (27.7 ml) at 25-30 C. The reaction mixture was heated to 80-85 C. and stirred for 8 irs at the same temperature. Cooled the reaction mixture to 25-30 C. Toluene (100 ml) was added to the reaction mixture and stirred for 45 minutes at 25-30 C. Filtered the reaction mixture and washed with toluene. Water was added to the filtrate. Basifying the reaction mixture with aqueous sodium carbonate solution. Both the organic and aqueous layers were separated and aqueous layer was washed with toluene. Dichloromethane was added to the aqueous layet AcidiFying the reaction mixture using Conc.HC1. Both the organic and aqueous layers were separated. Aqueous layer was extracted with dichioromethane and distilled off the solvent from the organic layer completely under reduced pressure to get the title compound; Yield: 109.6 gm.
With hydrogen; In water; at 80℃; under 22502.3 - 75007.5 Torr; for 12h;Autoclave;
Example 2 Preparation of Adipic Acid A 250 mL stirred autoclave was charged with a suspension of 24 g of the cis,cis-muconic acid and 1 g of Raney Ni in 56 g of water, hydrogen was injected to 3 MPa and the autoclave was heated to 80 C. On attainment of the temperature of 80 C., the pressure was increased to 10 MPa and a sufficient amount of further hydrogen was metered in to keep the pressure constant. After a reaction time of 12 h, the autoclave was cooled to a temperature of 60 C. and decompressed to standard pressure, and the catalyst was filtered out of the solution. Thereafter, the mixture was cooled gradually to 20 C., in the course of which adipic acid crystallized out as a white solid. In the solution, as well as adipic acid, it was still possible to detect lactone (V). The yield of adipic acid was 95% and that of lactone ( V) 5%. The mother liquor was recycled into the hydrogenation.
With 2% Rh/C; hydrogen; In water; at 80℃; under 37503.8 Torr;pH 3;Autoclave;
15 g of 2% Rh/C catalyst were suspended in 150 mL of water and the suspension was introduced into a 250 mL reactor. The suspension was stirred (700 rpm) and heated to 80 C. (internal reactor temperature). This temperature was kept constant over the reaction time by means of a temperature control device mounted in the reactor. 30 g/hour of a 33% by weight suspension of cis,cis-muconic acid in water and 50 standard liters/hour of hydrogen gas were conducted continuously into the reactor. At the same time, liquid and excess gas were conducted continuously out of the reactor, and the liquid volume and the pressure (about 50 bar) in the reactor were kept constant. Upstream of the discharge orifice, the reactor had a sintered metal frit (pore diameter 5 micrometres), which retained the suspended catalyst particles and muconic acid particles in the reactor. Beyond the discharge orifice was the discharge line. The discharge line had a valve which was used to decompress the mixture of discharged reaction mixture and discharged gas to standard pressure at 80 C. The pH of the reaction solution, measured at 60 C., was about 3. In total, about 5 kg of the cis,cis-muconic acid suspension were converted in the reactor. The liquid discharged was analyzed by means of 1H NMR spectroscopy. According to 1H NMR analysis, the discharged liquid, after removal of the water, comprised 96% by weight of adipic acid, 0.5% by weight of muconic acid, 2% by weight of dihydromuconic acid and 1% by weight of lactone I. Subsequently, the liquid discharged was purified by crystallization, or a post-hydrogenation was conducted with subsequent crystallization. (0216) Crystallization: (0217) The liquid discharged from the reactor was purified by crystallization. For this purpose, 1 kg of liquid discharged was cooled gradually from 60 C. to 20 C., in the course of which adipic acid crystallized out. The crystals were filtered off and dried. About 300 g of adipic acid were obtained with a purity of 99.85%. The adipic acid thus obtained was dissolved in 600 g of water, the solution was heated to 80 C. and the solution was cooled gradually to 20 C., in the course of which the adipic acid crystallized out. The crystals were filtered off and dried. About 270 g of adipic acid were obtained with a purity of 99.92%. The mother liquors were each recycled into the hydrogenation. (0218) Post-Hydrogenation and Crystallization: (0219) The liquid discharged from the reactor was post-hydrogenated and purified by crystallization. 4 kg of the liquid discharged were post-hydrogenated in a trickle bed reactor at hydrogen pressure 50 bar over 200 mg of 2% Rh/C at 150 C. In the course of this, the trickle bed reactor was supplied with 50 g/hour of the liquid discharged and 20 standard liters of hydrogen gas/hour. In the reaction output from the trickle bed, it was no longer possible to detect any ethylenically unsaturated compounds by 1H NMR analysis. The liquid discharged from the trickle bed reactor was cooled to 80 C. and the liquid was cooled gradually to 20 C., in the course of which adipic acid crystallized out. The crystals were filtered off and dried. About 310 g of adipic acid were obtained with a purity of 99.95%.
4.85 g (1.05 Eq.) of adipic acid was added to 10 ml of methanol in a 1L-three-neck flask, and a solution of amlodipine (13 g, 0.0316 mol) in 65 ml of methanol was added to the solution of adipic acid in methanol, followed by stirring at 23C for 2 hours. The reaction mixture was cooled to 7 C, stirred for one hour, and then filtered. The resulting solid was washed at 5 C with 15 ml of methanol and 15 ml of acetone, filtered, and then vacuum-dried at 35 C. As a result, a white, crystalline adipic acid salt of amlodipine was obtained in an amount of 15.5 g (yield: 91 %). The results of elementary analysis for the obtained crystalline adipic acid salt of amlodipine are shown in Table 1. [Table 1]
91%
In methanol; at 7 - 23℃; for 3h;
4.85 g (1.05 Eq.) of adipic acid was added to 10 ml of methanol in a 1L-three-neck flask, and a solution of amlodipine (13 g, 0.0316 mol) in 65 ml of methanol was added to the solution of adipic acid in methanol, followed by stirring at 23 C. for 2 hours. The reaction mixture was cooled to 7 C., stirred for one hour, and then filtered. The resulting solid was washed at 5 C. with 15 ml of methanol and 15 ml of acetone, filtered, and then vacuum-dried at 35 C. As a result, a white, crystalline adipic acid salt of amlodipine was obtained in an amount of 15.5 g (yield: 91%). [0041] The results of elementary analysis for the obtained crystalline adipic acid salt of amlodipine are shown in Table 1. [TABLE-US-00001] TABLE 1 Elemental analysis (C26H35CIN2O8) Unit (%) Measured value C: 55.9 H: 6.4 N: 5.1 O: 24.1 Calculated value C: 56.3 H: 6.4 N: 5.1 O: 26.0 [0042] Measurement was made in a temperature range of 50 to 200 C. with raising temperature at a rate of 1 C./min, using a melting-point measurement method (1) described in ?General Provisions of Preparations? of Korea Pharmacopoeia, 8th Ed., or a capillary method described in European Pharmacopoeia, 4th Ed., and the melting-point of the crystalline adipic acid salt of amlodipine measured was 164 to 168 C. [0043] The crystalline adipic acid salt of amlodipine was also subjected to X-ray powder diffraction, and the results are shown in FIG. 1, illustrating that it shows X-ray diffraction peaks at angles of 10.85, 13.02, 15.10, 16.31, 18.21, 21.69, 23.70, 26.18, and 28.74. The SEM photograph of the crystalline adipic acid salt of amlodipine is shown in FIG. 2.
EXAMPLE X Synthesis of Fluorinated Polymer of the Formula (III) Where t is 0.86, x is 0.14, q is 8 and s is 6 and the Ratio q to r is 1.3 to 1 Portions of 0.1 mol adipic acid were slowly added to a stirring mixture of 40 ml absolute ethanol and 0.1 mol <strong>[13093-04-4]N,N'-dimethyl-1,6-hexanediamine</strong> at 60 C., and then the reaction was raised to 80 C. for 1 hour. Crude nylon salt was obtained by rotoevaporation of the ethanol and layer-like crystal nylon salt was prepared by recrystallizing in a small amount of ethanol (10 ml) twice followed by drying in a vacuum oven at room temperature.
EXAMPLE 9 Preparation of dioctyltin adipate from adipic acid Adipic acid and dioctyltin oxide are introduced into a screw drier in accordance with Example 4b. At the exit, dioctyltin adipate (compound 6) is obtained as a white free-flowing powder.
5-(1-methyl-3,4,5,6,7,7-hexachloro-norborn-4-ene-1)-isophthalic acid dichloride[ No CAS ]
[ 77-40-7 ]
[ 111-50-2 ]
[ 124-04-9 ]
Yield
Reaction Conditions
Operation in experiment
In sodium hydroxide; hexane;
EXAMPLE X To prepare a co-polyphenyl ester of 5-(1-methyl-3,4,5,6,7,7-hexachloro-norborn-4-ene-1)-isophthalic acid and adipic acid, a solution of 0.516 grams (0.001 mole) of 5-(1-methyl-3,4,5,6,7,7-hexachloro-norborn-4-ene-1)-isophthalic acid dichloride and 0.732 grams (0.004 mole) of adipoyl chloride in 25 milliliters of n-hexane was added to a solution of 1.205 grams (0.005 mole) of <strong>[77-40-7]Bisphenol B</strong> in 40 milliliters of 1 Molar sodium hydroxide in a Waring blender at 30 C. The white copolymer was filtered, washed and dried. The product weighed 2.0 grams for a yield of 96 percent. It melted at 178 C.
6-methoxy-8-(1-piperazinyl)quinoline adipate salt[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
55%
Example 1; Preparation of 6-methoxy-8-[4-(l-(5-fluoro)-quinoIin-8-yl-pperidin-4-yI)-piperazin-l- yl]-quinoline (free base) Step 1: 6-Methoxy-8-(l-piperazinyl)quinolineA mixture of 8-amino-6-methoxyqumoline (150.0 g, 0.862 mol) and bis(2- chloroethyl)amine (219 g, 1.23 mol) in 6 parts (volume of hexanol v. weight of 8-amino-6- methoxyquinoline) of 1-hexanol (900 mL) was heated to 145 0C and stirred for 21 hours. Upon completion, the reaction mixture was cooled to 50 - 600C and 507 g of aqueous NaOH solution was added slowly. The reaction mixture was cooled to 25 - 30 0C and isopropyl acetate (750 mL) was added. The mixture was clarified through a Celite pad. The aqueous phase was then split off. The organic solution was treated with a slurry of adipic acid (126 g, 0.862 mol) in isopropyl acetate (250 mL). The resulting mixture was stirred for 16 hours to form 6-methoxy-8-(l-piperazinyl)quinolme adipate salt. The adipate salt was filtered and washed with isopropyl acetate (2x150 mL) and dried by nitrogen flow to give adipate of 6- methoxy-8-piperazin-l-yl-quinoline (186 g, 55% yield) with -97% HPLC area, 88% strength purity in 51% yield.
55%
A mixture of <strong>[90-52-8]8-amino-6-methoxyquinoline</strong> (150.0 g, 0.862 mol) and bis(2- chloroethyl)amine (219 g, 1.23 mol,) in 6 parts (volumerweight; hexanol:8-amino-6- methoxyquinoline) of 1-hexanol (900 mL) was heated to 145 0C and stirred for 21 hours. Upon completion, the reaction mixture was cooled 50 - 60 0C, and 507 g of aqueous NaOH solution (made from 300 g of water and 207 g of 50% NaOH) was added slowly. The reaction mixture was cooled to 25 - 30 0C and isopropyl acetate (750 mL) wass added.[02571 The mixture was then clarified through a celite pad. The aqueous phase was subsequently split off, and discarded. The organic solution was treated with a slurry of adipic acid (126 g, 0.862 mol) in isopropyl acetate (250 ml). The resulting mixture was <n="73"/>stirred for 16 hours to form 6-methoxy-8-(l-piperazinyl)quinoline adipate salt. The adipate salt was filtered and washed with isopropyl acetate (2x150 ml) and dried by nitrogen flow to give adipate of 6-Methoxy-8-piperazin-l-yl-quinoline (186 g, 55% yield) with -97% HPLC area, 88% strength purity in 51% yield.[0258] The salt was recrystallized from a mixture of methanol and isopropyl acetate. This was done due to the need for further purification. However, if purification is not required, the following procedure can be eliminated.[0259] To purify the adipate salt, 580 g of the crude adipate salt and 2.8 liter of methanol were mixed and heated to 65 0C and a dark solution was obtained. To this solution was charged slowly 1.1 liter of isopropyl acetate over 40 min at about 63 0C. The mixture was stirred at about 63 0C for about 1 h and cooled to 0-50C. After stirring at 0-5 0C for 2 hours, the mixture was filtered and washed with 300 ml of isopropyl acetate and dried with airflow. The total yield was 395 g, or 68.1% recovery.
20 g (4 molar equivalents) of <strong>[1115-70-4]metformin hydrochloride</strong> and 4.83 g (4 molar equivalents) of sodium hydroxide were stirred in a mixed solution of 180 ml of acetonitrile and 8 ml of water at room temperature, and then the produced inorganic salt was filtered. To the filtered solution, a solution of 4.41 g (1 molar equivalent) of adipic acid in acetonitrile-water was added dropwise and stirred at room temperature. The produced crystal was filtered and dried in hot air, thus obtaining 12.63 g (yield: 103.43%) of metformin adipate.
97.7%
12.5 g (2.5 molar equivalents) of <strong>[1115-70-4]metformin hydrochloride</strong> and 3.02 g (2.5 molar equivalents) of sodium hydroxide were stirred in a mixed solution of 112.5 ml of <n="27"/>tetrahydrofuran (THF) and 5 ml of water at room temperature, and then the produced inorganic salt was filtered. To the filtered solution, a solution of 4.41 g (1 molar equivalent) of adipic acid in tetrahydrofuran (THF)-water was added dropwise and stirred at room temperature. The produced crystal was filtered and dried in hot air, thus obtaining 11.94 g (yield: 97.7%) of metformin adipate
92.3%
Example 15 Preparation of Metformin Adipate 20.0 g of <strong>[1115-70-4]metformin hydrochloride</strong> and 4.83 g of sodium hydroxide were stirred in a mixed solution of 180 ml of acetone and 8 ml of water at room temperature, and then the produced inorganic salt was filtered. To the filtered solution, a solution of 4.41 g of adipic acid in acetone-water was added dropwise and stirred at room temperature. The produced crystal was filtered and dried in hot air, thus obtaining 11.26 g (yield: 92.3%) of metformin adipate.
90.2%
40.0 g of <strong>[1115-70-4]metformin hydrochloride</strong> and 9.66 g of potassium hydroxide were stirred in a mixed solution of 360 ml of acetone and 16 ml of water at room temperature, and then the produced inorganic salt was filtered. To the filtered solution, a solution of <n="25"/>8.82 g of adipic acid in acetone-water was added dropwise and stirred at room temperature. The produced crystal was filtered and dried in hot air, thus obtaining 22.01 g (yield: 90.2%) of metformin adipate.
89.6 - 92.3%
20.0 g of <strong>[1115-70-4]metformin hydrochloride</strong> and 4.83 g of sodium hydroxide were stirred in a mixed solution of 180 ml of acetone and 8 ml of water at room temperature, and then the produced inorganic salt was filtered. To the filtered solution, a solution of 4.41 g of adipic acid in acetone- water was added dropwise and stirred at room temperature. The produced crystal was filtered and dried in hot air, thus obtaining 11.26 g (yield: 92.3%) of metformin adipate.; 12.5 g (2.5 molar equivalents) of <strong>[1115-70-4]metformin hydrochloride</strong> and 3.02g (2.5 molar equivalents) of sodium hydroxide were stirred in a mixed solution of 112.5 ml of acetone and 5 ml of water at room temperature, and then the produced inorganic salt was filtered. To the filtered solution, a solution of 4.41 g (1 molar equivalent) of adipic acid in acetone-water was added dropwise and stirred at room temperature. The produced crystal was filtered and dried in hot air, thus obtaining 10.95 g (yield: 89.6%) of metformin adipate.
80.5%
With sodium hydroxide; In ethanol; at 70℃;Product distribution / selectivity;
10.00 g of <strong>[1115-70-4]metformin hydrochloride</strong>, 2.40 g of sodium hydroxide and 2.20 g of adipic acid were stirred in 150 ml of ethyl alcohol at 70 C , and then methylene chloride was added thereto. Then, the produced inorganic salt was filtered, and ethyl acetate was added to the filtrate. The produced crystal was filtered and dried in hot air, thus obtaining 4.90 g (yield: 80.5%) of metformin adipate.
In tetrahydrofuran;Product distribution / selectivity;
176 mg of <strong>[71125-38-7]meloxicam</strong> was ground with 37 mg of adipic acid and 400 muL of THF was added to the solid mixture. The solids gathered after grinding were stored in screw cap vials for subsequent analysis.
6-methoxy-8-(1-piperazinyl)quinoline adipate salt[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
55%
1) 6-methoxy-8-(1-piperazinyl)quinoline A mixture of <strong>[90-52-8]8-amino-6-methoxyquinoline</strong> (150.0 g, 0.862 mol) and bis(2-chloroethyl)amine (219 g, 1.23 mol,) in 6 parts (volume of hexanol vs weight of <strong>[90-52-8]8-amino-6-methoxyquinoline</strong>) of 1-hexanol (900 mL) was heated to 145 C. and stirred for 21 hours. Upon completion, the reaction mixture is cooled 50-60 C., and 507 g of aqueous NaOH solution was added slowly. The reaction mixture was cooled to 25-30 C. and isopropyl acetate (750 mL) was added. The mixture was clarified through a celite pad. The aqueous phase was then split off. The organic solution was treated with a slurry of adipic acid (126 g, 0.862 mol) in isopropyl acetate (250 ml). The resulting mixture was stirred for 16 hours to form 6-methoxy-8-(1-piperazinyl)quinoline adipate salt.
In ethyl acetate; at 0℃; for 4h;Product distribution / selectivity;
Example 3; <strong>[106133-20-4]Tamsulosin</strong> base (10.0 g, 24.48 mmol) and ethyl acetate (200 ml) are heated at reflux temperature until all solid is dissolved. Adipic acid (3.6 g, 24.63 mmol) is added to the solution and stirred until completely dissolved. Then the formed solution is slowly (in about two hours) cooled down to 0 C. Spontaneously clear white solid is obtained and the mixture is diluted with diethyl ether (200 ml). The formed mixture is stirred for another two hours at 0 C, filtered, washed with fresh diethyl ether and dried in vacuum at 40 C. 23.46 g of anhydrous tamsulosin adipate is obtained (95.8 % yield), m. p. 95-97 C, DSC onset 103.48 C.
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-1,2-dihydro-2-oxo-3H-indol-3-ylidine)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide, L-malic acid and adipic acid[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In 1,4-dioxane; water; for 0.05h;Reflux;
Example 8: Preparation of composition of <strong>[557795-19-4]sunitinib</strong>, L-malic acid and adipic acid (form Gamma 6)[00070] <strong>[557795-19-4]Sunitinib</strong> malate (150 mg, Form I) was dissolved in boiling dioxane/water (10 ml, 1 : 1). Adipic acid (55 mg, molar ratio of components is 1 : 1 : 1) was added. The resulting mixture was heated to reflux for 3 min, and then allowed to cool. The mixture was further cooled to -30C, and the resulting frozen mixture was lyophilized at 1 mBar.
With Oxone; In water; acetonitrile; for 36h;Reflux;
General procedure: To 16 mL of acetonitrile/water (1:1 v/v) mixture was added 0.5-1.2 mmol of the starting compound. The contents were heated at reflux with introduction of oxone (cf. entries for each case) incrementally over the entire duration of the reaction. For secondary benzyl halides, the reactions were run at room temperature. The progress of the reaction in each case was monitored by TLC analysis. After completion of the reaction, the reaction mixture was cooled to room temperature and the organic matter was extracted with ethyl acetate. The combined organic extract was dried over anhyd Na2SO4 and concentrated in vacuo. Short pad silica gel column chromatography of the residue led to isolation of the pure product.
3.0 g 16.9 millimoles/ of <strong>[183319-69-9]erlotinib hydrochloride</strong> are intensively stirred in the mixture of 100 ml of ethyl acetate, 60 ml of water and 30 ml of a concentrated ammonium hydroxide solution for 30 minutes /Heidolph MR 3001 , 1000 rpm/ at 50C. The phases are separated and the strongly alkaline aqueous layer is washed twice with 80 ml of ethyl acetate each and thereafter with 50 ml ethyl acetate at 50C the solution layers are well separated and are completely clear. The united ethyl acetate phases are washed four times with 100 ml of water each at the above temperature /the duration of each washing step is 15 minutes/. After each washing step clear well-separated phases are obtained. Finally the ethyl acetate phase is washed with 100 ml of a saturated sodium chloride solution, which is then dried over sodium sulfate and the drying agent is filtered off. Thus 310 ml /total volume/ of a solution are obtained which can be used in the salt forming reactions. a) Salt formation with maleic acid /preparation of the compound of the Formula 2/To the 310 ml of the ethyl acetate solution thus obtained a solution of 0.81 g (6.98 millimoles) of maleic acid and 10 ml of ethanol is added under intensive stirring /Heidolph MR 3001 , 1000 rpm/ at room temperature. The precipitation of crystals begins, whereupon the mixture is stirred for a further period of 24 hours, the precipitated crystals are filtered, washed with 20 ml of tert. butyl methyl ether and dried at 50C under a pressure of 160 mbar for 20 hours. Yield: 3.17 g (89 %). b) Salt formation with adipinic acid /preparation of the compound of the Formula 5/One proceeds according to point a) except that to the ethyl acetate solution 1.02 g (6.98 millimoles) of adipinic acid in 20 ml of ethanol is added. Crystallization is started by using a seeding crystals and external ice-water cooling. After the beginning of the crystal precipitation the mixture is stirred for a further period of 24 hours. The precipitated crystals are filtered, washed with 20 ml of tert. butyl methyl ether and dried at 50C under a pressure of 160 mbar for 20 hours.Yield 2.71 g (72 %).
Into an apparatus 10 ml of ethanol are weighed in under intensive stirring whereupon 0.604 g /l .54 millimoles/ of <strong>[183321-74-6]erlotinib</strong> base are dissolved therein under reflux. To the reaction mixture at this temperature a solution of 0.225 g l .54 millimoles/ of adipinic acid in 5 ml of ethanol is added under stirring. The reaction mixture is allowed to cool to room temperature under stirring while the precipitation of crystals begins already in the warm solution, The precipitated product is filtered and washed with tertiary butyl methyl ether. The product is dried at room temperature on the air for a day.Yield: 0.70 g (84 %).The crude product thus obtained is recrystallized from 25 ml of isopropanol. The precipitate is filtered and washed with a small amount of cold isopropanol and tertiary butyl methyl ether. Thus 0.55 g (78 %) of a white crystalline product is obtained.Mp.: 150.3-154.0CAnalysis for the Formula C22H23N304 · C6Hi0N3O4 (539.59):Calc: C: 62.33 H: 6.16 N: 7.79Found: C: 62.63 H: 6.29 N: 7.69 IR (KBr, cm-1): 3254, 2929, 2456, 1606, 1574, 1515, 1446, 1327, 1286, 1128, 1073, 1035. ?-NMR 400 MHz): 12.00 (b, 2H), 9.46 (b, 1H), 8.51 (s, 1H), 8.01 (m, 1H), 7.92 (m, 1H), 7.87 (s, 1H), 7.41 (m, 1H), 7,23 (s, 1H), 7.22 (m, 1H), 4.30 (m, 4H), 3.80 (m, 2H), 3.76 (m, 2H), 3.39 (s, 3H), 3.37 (s, 3H), 2.21 (m, 4H), 1.52 (m, 4H).,3C-NMR (DMSO- , 100 MHz): 174.46, 156.29, 153.88, 152.93, 148.33, 147.17, 139.98, 129.02, 126.49, 124.91, 122.70, 121.92, 109.1 1, 108.40, 103.45, 83.67, 80.61, 70.31, 70.24, 68.59, 68.23, 58.56, 33.56, 24.21.
5-chloro-3-(4-methanesulfonylphenyl)-6'-methyl-[2,3']bipyridinyl adipate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In isopropyl alcohol; at 65℃;
250mg 5-chloro-3-(4-methanesulfonylphenyl)-6'-methyl-[2,3']bipyridinyl and 102 mg of adipic acid were dissolved in 15ml of isopropanol at 65C to give a slightly yellow solution. The solution was cooled to room temperature then allowed to evaporate to yield the desired adipic acid salt as a white powder.
To a 10 mL glass peptide synthesis vessel was added Rink Amide AM resin (0.60 g, 0.31 mmol)and DMF (4 mL). The mixture was gently agitated with a wrist-action Burrel shaker for 1h andthen filtered. A 20% solution of piperidine in DMF (4 mL) was added and the mixture wasagitated for 30 min. The resin was filtered and then washed with DMF (3 × 4 mL). 7-N-(Fluorenylmethoxycarbonyl)aminocoumarin-4-acetic acid1 (0.40 g, 0.91 mmol), HOBt.H2O (140mg, 0.95 mmol) and DMF (4 mL) was added to the resin followed by DIC (144 muL, 0.93 mmol).The mixture was agitated for 24h, filtered and then washed with DMF (3 × 4mL), THF (3 × 4mL)and MeOH (3 × 4mL) respectively.General Procedure for Coupling the First Fmoc-Amino Acid to the ACC-ResinTo a 10 mL glass peptide synthesis vessel was added ACC-resin (0.31 mmol) and DMF (4 mL).The mixture was gently agitated with a wrist-action Burrel shaker for 1h and then filtered. A 20%solution of piperidine in DMF (4 mL) was added and the mixture was agitated for 30 min. Theresin was filtered and then washed with DMF (3 × 4 mL). In a separate scintillation vial wereadded Fmoc-amino acid (1.32 mmol), HOBt (200 mg, 1.32 mmol), DMF (4 mL) and DIC (200 muL,1.29 mmol). After a preactivation time of 5 min, the mixture was added to the resin and agitatedovernight. The resin was filtered and washed with DMF (3 × 4 mL).Representative Synthesis of a Di-peptide -ACCAs a representative example, the synthesis of N-suc-L-Phe-Gly-ACC is described. To a 10 mLglass peptide synthesis vessel was added Fmoc-Gly-ACC-resin (0.1 mmol) and DMF (3 mL). The mixture was gently agitated for 1h and then filtered. A 20% solution of piperidine in DMF (3mL) was added and the mixture was agitated for 30 min. The resin was filtered and then washedwith DMF (3 × 3 mL). In a separate scintillation vial were added Fmoc-L-Phe-OH (190 mg, 0.5mmol), HOBt (76 mg, 0.5 mmol), DMF (3 mL) and DIC (76 muL, 0.5 mmol). After a preactivationtime of 5 min, the mixture was added to the resin and agitated for 5h. The resin was filtered andwashed with DMF (3 × 4 mL). A 20% solution of piperidine in DMF (3 mL) was added and themixture was agitated for 30 min. The resin was filtered and then washed with DMF (3 × 3 mL).Succinic anhydride (100 mg, 1.0 mmol), DMF (3mL) and DIPEA (150 muL, 0.9 mmol) were addedand the mixture was agitated overnight, filtered and then washed with DMF (3 × 4 mL). Asolution of TFA:iPr3SiH:H2O (95:2.5:2.5, 3 mL) was added and the mixture was agitatedovernight. The resin was filtered and washed with TFA (2 × 3 mL). The combined filtrate wasconcentrated and the residue was washed with ether (3 × 3 mL) to give suc-L-Phe-Gly-ACC aspale yellow solid (32 mg, 62%). Amino terminus of some peptides was capped as the acetylderivative. This was accomplished by premixing AcOH (5 equiv), HOBt (5 equiv) and DIC (5equiv) in DMF and adding the mixture to the resin. The resulting mixture was agitated for 5h,filtered, and then washed with DMF. For ACC-peptides 11-18, the amino terminus was coupledwith the corresponding dicarboxylic acid as follows: In a separate scintillation vial were addeddicarboxylic acid (5 equiv), HOBt (5 equiv), DMF and DIC (5 equiv). After a pre-activation time of5 min, the mixture was added to the resin and agitated overnight. The resin was filtered andwashed with DMF (3 × 4 mL). The purification of all ACC-peptides was performed either bysimply washing the solid thoroughly with ether or by reverse-phase HPLC (ACN/H2O-0.1% TFA,15 - 60% for 20 min, 20 mL/min, 254 nm detection for 22.5 min). Purity check for all ACCpeptideswas completed by analytical reverse-phase HPLC (ACN/H2O-0.1% TFA, 10 - 60% for20 min, 1 mL/min, 254 nm detection for 23 min). Retention times are indicated as tR.
[{Cu(μ4-(adipic acid(-2H)))(N-methylnicotinamide)}n*nH2O][ No CAS ]
Yield
Reaction Conditions
Operation in experiment
74%
for 24h;
The compound 5 was prepared by the reaction of an aqueoussolution (1:1) of copper(II) acetate monohydrate (1 mmol,0.200 g) in 50 cm3 with N-methylnicotinamide (2 mmol, 0.272 g) followed by an addition of the adipic acid (2 mmol,0.292 g). The green reaction mixture was stirred for 1 day andthen left to slowly evaporate at ambient temperature. Wellshapedgreen crystals, suitable for X-ray single-crystal structuralanalysis, were collected after a few days by filtration, washedwith water and finally dried at ambient temperature. Yield:0.27 g (74 %).Anal calc. for C13H18CuN2O6 (Mr = 361.83): C43.15, H 5.01, N 7.74. Found: C 43.24, H 4.98, N 7.80 %.
6-[1-(2-nitrophenyl)ethoxy]-6-oxohexanoic acid[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
66%
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; N,N-dimethyl-formamide; at 0 - 25℃;Inert atmosphere;
Adipic acid (6 g, 41.1 mmol), was dissolved in minimal DMF, DCM was added (1:1 vol), and the solution was cooled to 0 °C. 1-(2-nitrophenyl) ethanol (2.3 g, 13.7 mmol) and cat. DMAP were added. Last, EDCI (3.9 g, 20.5 mmol) was added to the mixture and the reaction was stirred overnight warming up to RT. The solution was taken up into EtOAc (200 mL) and washed with water, 1N HCl, and sat. NH4Cl solution. The organic layer was dried over Na2SO4. The volatiles were evaporated and the residue was purified on silica gel chromatography (gradient EtOAc:hexanes, 1:2-1:1), affording product 2a as a white thick oil in 66percent yield. 1H NMR (300 MHz, CDCl3): delta = 1.58-1.72 (m, 7 H), 2.31-2.40 (m, 4 H), 6.32 (q, 1 H, J = 6.6 Hz), 7.41-7.47 (m, 1 H), 7.62-7.68 (m, 2 H), 7.93 (d, 1 H, J = 8.1 Hz). 13C NMR (75 MHz, CDCl3): delta = 21.9, 23.9, 24.1, 33.6, 33.8, 68.0, 124.4, 127.2, 128.4, 133.6, 137.8, 147.7, 172.2, 179.5. HRMS: m/z calcd for C14H17NO2 [M + Na]+: 318.0954; found: 318.0966.
With hydrogen; In water; at 80℃; under 22502.3 - 75007.5 Torr; for 12h;Autoclave;
10184] A 250 mL stirred autoclave was charged with a suspension of 24 g of the cis,cis-muconic acid and 1 g of Raney Ni in 56 g of water, hydrogen was injected to 3 MPa and the autoclave was heated to 80 C. On attainment of the temperature of 80 C., the pressure was increased to 10 MPa and a sufficient amount of further hydrogen was metered in to keep the pressure constant. After a reaction time of 12 h, the autoclave was cooled to a temperature of 60 C. and decompressed to standard pressure, and the catalyst was filtered out of the solution. Thereafter, the mixture was cooled gradually to 20 C., in the course of which adipic acid crystallized out as a white solid. In the solution, as well as adipic acid, it was still possible to detect lactone (V). The yield of adipic acid was 95% and that of lactone (V) 5%.
A process for preparing an OB acid, comprising the steps of: 1, Check the synthesis reactor. All pipelines and valves are intact. Will have been cleaned of the reactor and the condenser in the case of exhaust gas drying. The temperature was then lowered to 40 C. 2, Open the manhole cover. Into the reactor, 365 kg of adipic acid and 8 kg of 4-dimethylaminopyridine were charged under vacuum. Cover the manhole cover. 3500 kg of thionyl chloride was vacuumed. 3, After feeding, after standing for 6 min, open the reactor jacket and condenser cooling water. Stir in the exhaust vent conditions 0.5h. 4, Jacket into the cold water. Improved steam. Heat the mixture with hot water. 5, The material temperature was increased to 78 C (15 C / h) for 3.5 h. 6, Between 78 ~ 81 C and maintain a good reflux. 7, After the reflux of the thionyl chloride, row of jacket hot water. Into the steam slowly warming. With 21h time, the material temperature was raised to 110 C at an average rate of 3 C / h. Excessive release of thionyl chloride was initiated. 8, After the temperature was increased to 120 C, the pressure was reduced by vacuum distillation using a water jet pump. Continue to discharge high-boiling-point by-products such as sulfur chloride. The temperature was then raised to 138 C to maintain the temperature. 9, Started to maintain temperature. Start the distillation water jet vacuum pump. The distillation system is preheated. To be maintained temperetaure to end. Discharge into the distillation kettle. 10, After all of the synthetic materials were transferred to a still kettle, open the receiving tank jacket cooling water. Start distilling kettle stirring. Under the action of water jet vacuum pump, the material temperature was slowly raised to 165 C over a period of 1.5 h. Gradually speed up the heating rate. Increase the vacuum to 0.07MPa. The acid chloride was distilled under reduced pressure to distillate-free. 475 kg of acid chloride was obtained. 11, Open the decolorization kettle vacuum valve. The distillated acid chloride was heated to 70 C and 100 kg of water was added dropwise. The acid chloride was hydrolyzed to a completely solid. Add water to 2500L. Dropping 30% concentration of liquid sodium hydroxide, so that the solution pH value of 10. Jacket into the steam heated to 72 C and heat 2h. Re-test the pH value of 9.3. Cooled to 40 C. Transferred into the bleaching kettle. The pH of the solution was adjusted to 6.0 by the addition of hydrochloric acid. Stir until it is stable. Stop mixing. Into the kettle into the activated carbon. Decolorized with stirring at 80 C for 1 h. Into the cold water to 30 C. The solution was filtered through a filter. 12, Filtration of the filtrate into the acidification reactor. Dropping hydrochloric acid under stirring to bring the pH value of the solution to 2.0. Stirring 15min. Re-test with a precision test strip after feeding into the centrifuge rejection rejection filter. Filtrate into the sedimentation tank. The filter cake was dried and weighed. Was crude 365kg. 13, 11 times the weight of the crude product obtained, the crude product is put into a refining kettle under the action of stirring. Cover the man hole cover. Jacket over the steam quickly heated to reflux. Side by side hot water jacket to improve the cold water quickly cooled to 45 C filtration. Was refined products. 14, Will be refined after two refined products into enamel double cone dryer. Open the steam and vacuum. The baking was carried out at 110 C for 4.5 h under reduced pressure. The vacuum degree is 0.08MPa. After sampling analysis, moisture ? 0.20% qualified. Cooling. Remove the cold after crushing packaging. The finished product obtained in this example was 325 kg. HPLC analysis of the content of 99.13%. Yield: 75.58%.
With phosphorus pentoxide; phosphoric acid; tin(ll) chloride; at 140 - 210℃; for 8.0h;Inert atmosphere;
1, nitrogen was introduced into the reaction vessel, 9.78 g of phosphoric acid (85% phosphoric acid) and 19.47 g of P2O5 were mixed To form a polyphosphoric acid solution; 2. Weigh 4.3 g (0.0105 mol) 2,4-diaminophenol hydrochloride and 1.46 g (O.Olmol) adipic acid as Reaction of raw materials, polyphosphoric acid solution heated to 150 C mechanical stirring reaction 6 hours after the temperature to 130 C, to polyphosphate Was added 0.5 g of SnCl2 reducing agent, the control temperature of 140 C under the conditions of adding the reaction raw materials 2,4-diaminophenol hydrochloride and adipic acid, after 3 hours of reaction, the temperature was raised to 210 C, and the reaction product was obtained after 5 hours of reaction. 3, the reaction product with distilled water for washing, and by sodium carbonate and then washed until the product was neutral, Drying to obtain the initial product;; 4, the initial product with anhydrous ethanol extraction, and finally at 80 C vacuum drying 12h, get 2.9g sand color 2,2'-butylenebis [5-aminobenzoxazole] powder.
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 0 - 20℃; for 6h;Inert atmosphere;
General procedure: Adipic acid (1.00 g, 6.84mmol) and EDC (3.15g, 16.8 mmol) was dissolved in 50 mL dryCH2Cl2. The solution was allowed cool to 0 oC in ice bath, after which <strong>[769-39-1]tetrafluorophenol</strong> (<strong>[769-39-1]TFP</strong>-OH, 2.50 g,15.1 mmol) was added. The solution was allowed to warm to rt and stirred for 6 h. After removal of thesolvent under reduced pressure, the crude product was purified by flash column chromatography (PE/DCM1:1) on silica gel to give <strong>[769-39-1]TFP</strong> linker 5 (2.54 g, 84%) as white solid. 1H NMR (600 MHz, Chloroform-d) delta7.01 (t, J = 8.8 Hz, 2H), 2.77 (s, 4H), 1.94 (d, J = 4.8 Hz, 4H). 19F NMR (376 MHz, Chloroform-d) delta-138.40 - -140.13 (m), -152.79 - -153.62 (m). 13C NMR (101 MHz, Chloroform-d) delta 168.90 , 145.97 (dtd, J= 248.5, 11.9, 4.2 Hz), 140.53 (dddd, J = 250.4, 15.3, 4.8, 2.3 Hz), 129.80 - 129.23 (m), 103.19 (t, J = 22.8Hz), 32.87 , 23.84.
4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl}morpholin-3-one adipic acid[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
74.4%
2-({(5S) -2-oxo-3-[4- (3-oxo-4-morpholinyl) phenyl] -1,3-oxazolidin-5- yl} methyl)-1,3(2H) -dione (Formula 5) were added 75 ml of ethanol and 8.1 ml of a methylamine solution (concentration in water 40%) was added.The reaction mixture was then diluted with 60In Heating, Stir at this temperature for 2 hours.Confirm that the reaction is completed, and while maintaining the temperature, dilute the solution with 50 ml of ethanol and 3.04 ml of phosphoric acid, and slowly add the solution to the reaction solution. After confirming that the crystallization of the product was initiated and cooling to 20 C, the precipitated reaction product was filtered under suction. The resulting solid was dispersed in 110 ml of methanol, refluxed for 30 minutes and stirred, and then cooled to room temperature. The resulting crystals were filtered,And dried at 50 DEG C for 4 hours to obtain 11.1 g of morpholine diphosphate (Formula 2). (Yield: 96.0%)
7-cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide adipate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In water; acetone; at 20℃;
200mg of compound I freebase powder was addedinto 10.0 mL of acetone/water (v/v=19/1), and 68 mg of adipic acid was added to the solution, then stirred at room temperature, the solid was obtained. The ?H NMR spectrum is displayed in FIG. 22.?H NMR data of adipate Form A produced in this example is shown as following: ?H NMR (400 MHz, DMSO) oe 9.31 (s, 1H), 8.76 (s, 1H), 8.15 (d, J=9.1 Hz, 1H), 7.99 (d, J=2.8 Hz, 1H), 7.42 (dd, J=9.1, 3.0 Hz, 1H), 6.60 (s, 1H), 4.78-4.67 (m, 1H), 3.06 (d, J=4.9 Hz, 1OH), 2.95-2.82 (m, 4H), 2.48-2.38 (m, 2H), 2.25-2.09 (m, 4H), 1.98 (s, 4H), 1.64 (d, J=4.9 Hz, 2H),1.54-1.38 (m, 4H). The result shows the solid is adipate Form A. The XRPD data of the adipate Form A produced in this example are listed in Table 7. The XRPD pattern is displayed in FIG.13, the DSC curve is displayed in FIG. 14, the TGA curve is displayed in FIG. 15.
<strong>[404950-80-7]Panobinostat</strong> base (2.0 g) and adipic acid (1.05 eq.) are dissolve in methanol (20.0 ml). The clearsolution was evaporated to obtain solid. XPRD of the solid gives pure amorphous form of<strong>[404950-80-7]Panobinostat</strong> adipate.
General procedure: <strong>[2364-75-2]Emoxypine</strong> and dicarboxylic acid in a 1:1 molar ratio weredissolved in a methanol-acetone mixture (1:1 v:v) and stirreduntil a clear solution was obtained. The solution was kept in afume hood at room temperature. Diffraction-quality crystalsof the <strong>[2364-75-2]emoxypine</strong> salts were grown over a period of 3-4 d. Thecrystals obtained from the crystallization batches were dried inair before being subjected to further analysis.
0.44 g (3 mmol) of adipic acid was dissolved in 15 ml of anhydrous dioxane, and after adding 0.25 g (2.5 mmol) of triethylamine, 0.28 g (2.4 mmol) of thionyl chloride was added dropwise, and vacuum nitrogen was added dropwise. Protected, refluxed at 110 C for 4 h, concentrated the reaction mixture under reduced pressure to give a pale yellow oil.Reconstituted with 10 ml of DMF. 0.78 g (3.2 mmol) of <strong>[95058-81-4]gemcitabine</strong> was added, and 0.19 g (1.5 mmol) of triethylamine was added dropwise thereto at room temperature, and the mixture was subjected to vacuum nitrogen-protection overnight, and the reaction was completed by TLC. The reaction mixture was concentrated under reduced pressure to give a red brown oil. Column chromatography gave a white solid in 61% yield.
N,N’-bis({4-[(6-methoxyquinolin-8-yl)amino]pentyl})hexanediamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
65%
General procedure: PQdiphosphate(0.349 g, 0.766mmol) and TEA (0.428 mL, 3.211mmol) were stirred in dichloromethane (15 mL) to obtain PQ base.Dicarboxylicacid (succinic,fumaric, maleic,glutaric,adipic,pimelic,suberic, oritaconicacid) (0.333mmol) was activated using HATU (0.279, 0.733mmol) in the presence ofHuenig?sbase (DIEA) (0.255 mL, 1.465mmol) in dichloromethane (10 mL). After 15 min, a solution of PQ base was added to a solution of correspondingdicarboxylicacid and stirred overnight at room temperature. The solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate (30 mL) and extracted with brine (3 × 30 mL), dried over anhydrous sodiumsulfateand evaporated. The crude product was purified by column chromatography (mobile phase cyclohexane/ethyl acetate/methanol 1:1:0.5).