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[ CAS No. 52549-17-4 ] {[proInfo.proName]}

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Chemical Structure| 52549-17-4
Chemical Structure| 52549-17-4
Structure of 52549-17-4 * Storage: {[proInfo.prStorage]}
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Product Details of [ 52549-17-4 ]

CAS No. :52549-17-4 MDL No. :MFCD00866111
Formula : C15H13NO3 Boiling Point : -
Linear Structure Formula :- InChI Key :TVQZAMVBTVNYLA-UHFFFAOYSA-N
M.W : 255.27 Pubchem ID :4888
Synonyms :
Y 8004;Pyranoprofen

Calculated chemistry of [ 52549-17-4 ]

Physicochemical Properties

Num. heavy atoms : 19
Num. arom. heavy atoms : 12
Fraction Csp3 : 0.2
Num. rotatable bonds : 2
Num. H-bond acceptors : 4.0
Num. H-bond donors : 1.0
Molar Refractivity : 70.12
TPSA : 59.42 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : Yes
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.9 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.82
Log Po/w (XLOGP3) : 2.75
Log Po/w (WLOGP) : 2.97
Log Po/w (MLOGP) : 2.22
Log Po/w (SILICOS-IT) : 2.95
Consensus Log Po/w : 2.54

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.56

Water Solubility

Log S (ESOL) : -3.49
Solubility : 0.0825 mg/ml ; 0.000323 mol/l
Class : Soluble
Log S (Ali) : -3.65
Solubility : 0.0568 mg/ml ; 0.000222 mol/l
Class : Soluble
Log S (SILICOS-IT) : -4.37
Solubility : 0.0109 mg/ml ; 0.0000429 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 0.0
Synthetic accessibility : 3.22

Safety of [ 52549-17-4 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 52549-17-4 ]

* 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.

  • Downstream synthetic route of [ 52549-17-4 ]

[ 52549-17-4 ] Synthesis Path-Downstream   1~56

YieldReaction ConditionsOperation in experiment
5 EXAMPLE 5 EXAMPLE 5 A mixture of 100 g of ethyl 2-cyano-2-2-(5H-[1]benzopyrano[2,3-b]-pyridin-7-yl)propionate, 500 ml of glacial acetic acid and 200 g of concentrated hydrochloric acid is refluxed for 48 hours. The reaction mixture is concentrated, and the residue is dissolved in hot water. The solution is adjusted to pH 2-3 by addition of 10% sodium hydroxide. The resulting crystalline precipitate is washed thoroughly with water, and recrystallized from aqueous dioxane to give 74 g of 2-(5H-[1]benzopyrano[2,3-b]pyridin-7-yl)propionic acid as white crystals melting at 183°-183.5°C. The starting compound ethyl 2-cyano-2-(5H-[1]benzopyrano[2,3-b]-pyridin-7-yl)propionate is prepared as follows:
  • 3
  • 7-(1-bromoethyl)-5H-[1]-benzopyrano[2,3-b]pyridine [ No CAS ]
  • [ 144-55-8 ]
  • [ 52549-17-4 ]
YieldReaction ConditionsOperation in experiment
In tetrahydrofuran 13 EXAMPLE 13 EXAMPLE 13 A Grignard reagent is prepared from 0.31 g of metallic magnesium and 2.9 g of 7-(1-bromoethyl)-5H-[1]benzopyrano[2,3-b]pyridine in 10 ml of anhydrous tetrahydrofuran. To the Grignard reagent is added a large excess of dry ice. The mixture is allowed to stand overnight, and then poured into diluted hydrochloric acid. The precipitate is filtered off, and added to an aqueous sodium bicarbonate solution. An insoluble material is removed by filtration, and the filtrate is made acid with acetic acid. The resulting white crystals are collected and recrystallized from aqueous dioxane to give 2-(5H-[1]benzopyrano[2,3-b]pyridin-7-yl)propionic acid melting at 182.5°-183.5°C.
  • 4
  • [ 52549-19-6 ]
  • [ 52549-17-4 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; sodium hydroxide; sodium borohydrid In water 9 EXAMPLE 9 EXAMPLE 9 4.75 g of 2-(5-oxo-5H-[1]benzopyrano[2,3-b]pyridin-7-yl)propionic acid is dissolved in a solution of 0.88 g of sodium hydroxide in 25 ml of water. To the solution are added 5 g of sodium borohydride and a small amount of toluene, and the mixture is heated under reflux for 3 hours. The reaction mixture is adjusted to pH 3 by adding concentrated hydrochloric acid under ice cooling. The resulting crystalline precipitate is filtered off, washed with water, and recrystallized from aqueous dioxane to give 2.5 g of 2-(5H-[1]benzopyrano[2,3-b]pyridin-7-yl)propionic acid as white needles melting at 182.5°-183.5°C.
  • 5
  • 2-(5H-[1]benzopyrano[2,3-b]pyridin-7-yl)propionaldehyde [ No CAS ]
  • [ 52549-17-4 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide In ethanol; water 7 EXAMPLE 7 EXAMPLE 7 2.4 g of 2-(5H-[1]benzopyrano[2,3-b]pyridin-7-yl)propionaldehyde is added in small portions to a mixture of 2.5 g of silver oxide, 50 ml of water, 50 ml of ethanol and 1.6 g of sodium hydroxide under cooling. The mixture is stirred for 30 minutes, and the silver produced is removed by filtration, and then the ethanol is distilled off. Water is added to the residue, and the resulting mixture is filtered to remove an insoluble material. The filtrate is adjusted to pH 3-4 by addition of hydrochloric acid. Thus 1.8 g of 2-(5H-[1]benzopyrano[2,3-b]pyridin-7-yl)propionic acid is obtained as precipitate. The product, when recrystallized from aqueous dioxane, melts at 182°-183°C.
  • 6
  • 2-(5H-[1]benzopyrano[2,3-b]pyridin-7-yl)acrylic acid [ No CAS ]
  • [ 52549-17-4 ]
YieldReaction ConditionsOperation in experiment
In sodium hydroxide; hydrogen 11 EXAMPLE 11 EXAMPLE 11 2.5 g of 2-(5H-[1]benzopyrano[2,3-b]pyridin-7-yl)acrylic acid is dissolved in 20 ml of 0.5 N aqueous sodium hydroxide soution, and 1 g of Raney nickel is added. The solution is stirred in a hydrogen stream at ordinary pressure and temperature until absorption of 230 ml of hydrogen is attained. The Raney nickel is removed by filtration, and the filtrate is neutralized with hydrochloric acid. The resulting crystalline precipitate is filtered off, washed with water, and recrystallized from aqueous dioxane to give 1.8 g of 2-(5H-[1]benzopyrano[2,3-b]pyridin-7-yl)propionic acid melting at 183°-184°C.
  • 7
  • 2-chloro-2-(5H-[1]benzopyrano[2,3-b]pyridin-7-yl)propionic acid [ No CAS ]
  • [ 52549-17-4 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide In hydrogen 12 EXAMPLE 12 EXAMPLE 12 A mixture of 2.9 g of 2-chloro-2-(5H-[1]benzopyrano[2,3-b]pyridin-7-yl)propionic acid, 40 ml of 0.5 N aqueous sodium hydroxide solution and 1 g of Raney nickel is stirred in a hydrogen stream at ordinary pressure and temperature, until absorption of 230 ml of hydrogen is attained. The RAney nickel is then filtered off, and the filtrate is neutralized with hydrochloric acid. The crystalline precipitate is filtered off, washed with water, and recrystallized from aqueous dioxane to give 1.5 g of 2-(5H-[1]benzopyrano-[2,3-b]pyridin-7-yl)propionic acid melting at 183°-184°C.
  • 8
  • cobalt(II) sulphate heptahydrate [ No CAS ]
  • [ 52549-17-4 ]
  • 2C15H12NO3(1-)*Co(2+) [ No CAS ]
YieldReaction ConditionsOperation in experiment
70.15% With sodium hydroxide In water at 160℃; for 72h; Autoclave; High pressure; 2.2 Synthesis of [Co(L)2]n (1) A mixture of CoSO4·7H2O (0.0280g, 0.1mmol), NaOH (0.0072g, 0.18mmol), HL (0.0194g, 0.1mmol) and water (6ml) were heated at 160°C for 3days in a 15ml Teflon-lined vessel container. The reaction mixture was cooled to room temperature at a rate of 5°Ch-1. The purple block crystals of complex 1 suitable for X-ray diffraction analysis were obtained (0.0398g, Yield: 70.15%) based on CoSO4. Elemental analysis calcd (%) for (567.44): C, 70.86; H, 4.76; N, 5.51; found: C, 70.71; H, 4.77; N, 5.50. IR (KBr, cm-1): 2957(w), 2924(w), 1624(s), 1498(m), 1449(vs), 1380(s), 1356(m), 1282(m), 1234(w), 1201(s), 1147(w), 1130(w), 1110(w), 903(w), 793(m), 758(w), 745(w), 704(w), 684(w), 555(w).
  • 9
  • [ 124-38-9 ]
  • 7-(1-chloroethyl)-5H-[1]-benzopyrano[2,3-b]pyridine [ No CAS ]
  • [ 52549-17-4 ]
YieldReaction ConditionsOperation in experiment
50% With iodine; magnesium In tetrahydrofuran at 65℃; for 1.5h; 10 Preparation of 2-(5H-[1]-benzopyrano[2,3-b]pyridin-7-yl)propanoic acid (11) 1 g of magnesium turnings, 0.1 g of iodine was added to 100 mL of tetrahydrofuran, a solution of 1 g of compound 9 in 5 mL of tetrahydrofuran was added dropwise under stirring, and the temperature was slowly raised to 65 ° C to initiate the reaction. Iodine red faded. A solution of 9 g of compound 9 in 45 mL of tetrahydrofuran was slowly added dropwise. After the dropwise addition, the reaction was heated to reflux for 1 hour. After falling to room temperature, the reaction solution was slowly poured onto 20 g of dry ice, stirred for 30 minutes to dry ice completely disappeared.concentrate,Add the water to dissolve the residue.With sodium hydroxide to adjust the pH greater than 10,The system was extracted with ethyl acetate (50 mL x 3)Collecting water,Decolorization with 0.5 g of activated carbon,filter. The filtrate was adjusted to pH 4 with glacial acetic acid,Precipitation of solids,Suction filter. The solid was recrystallized from a mixed solvent of 40 mL of ethanol and 40 mL of water, 5.2 g of white crystalline compound 11 in 50% yield.
  • 10
  • 7-(1-bromoethyl)-5H-[1]-benzopyrano[2,3-b]pyridine [ No CAS ]
  • [ 124-38-9 ]
  • [ 52549-17-4 ]
YieldReaction ConditionsOperation in experiment
49% With iodine; magnesium In diethyl ether at 45℃; for 1.5h; Inert atmosphere; 6 Preparation of 2-(5H-[1]-benzopyrano[2,3-b]pyridin-7-yl)propanoic acid (11) Under N2, magnesium (4.5 g) and iodine (0.5 g) were added to diethyl ether (150 mL), a small amount of compound 10 (5 g, 1/10 of the total amount) was added dropwise under mechanical stirring, heated to 45 ° C, stirred to reaction initiation (iodine red retreat), and the reaction system was maintained under the state of micro-reflow. The remaining compound 10 (45 g) was slowly added dropwise, heated to reflux for 1 hour and then cooled to room temperature, and then maintained in ice bath at -5 ± 5 oC, the temperature was maintained, CO2 gas (8 L) was added slowly, stirred for 30 minutes to complete the reaction. The system was concentrated and the residue was diluted with water (150 mL). Sodium hydroxide (6 g) was added to adjust pH greater than 10, dichloromethane (50 mL x 3) was added, the water phase was separated, decolorized with 1 g activated carbon, filtered and the pH of the filtrate was adjusted to 4 with acetic acid, white solids were precipitated, filtered, the solid was recrystallized from a mixed solvent of ethanol (50 mL) and water (50 mL) to give 22 g of white crystalline compound 11 in 49% yield.
  • 11
  • 7-(1-chloroethyl)-5H-[1]-benzopyrano[2,3-b] pyridin-5-one [ No CAS ]
  • [ 52549-17-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: lithium borohydride / methanol / 5 h / 60 °C 2: hydrogenchloride / water; isopropyl alcohol / 4 h / Reflux 3: magnesium; iodine / tetrahydrofuran / 1.5 h / 65 °C
  • 12
  • [ 2942-59-8 ]
  • [ 52549-17-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1: sodium hydroxide / methanol / 1.5 h / 170 - 180 °C 2: trichlorophosphate / 2 h / Reflux 3: N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) / dichloromethane / 6.5 h / Reflux 4: potassium borohydride / tetrahydrofuran; water / 3 h / 65 °C 5: hydrogen bromide / isopropyl alcohol / 5 h / Reflux 6: magnesium; iodine / diethyl ether / 1.5 h / 45 °C / Inert atmosphere
Multi-step reaction with 6 steps 1: sodium hydroxide / methanol / 1.5 h / 170 - 180 °C 2: trichlorophosphate / 2 h / Reflux 3: 2,2'-azobis(isobutyronitrile); N-chloro-succinimide / tetrachloromethane / 4.5 h / 20 °C 4: lithium borohydride / methanol / 5 h / 60 °C 5: hydrogenchloride / water; isopropyl alcohol / 4 h / Reflux 6: magnesium; iodine / tetrahydrofuran / 1.5 h / 65 °C
  • 13
  • [ 123-07-9 ]
  • [ 52549-17-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1: sodium hydroxide / methanol / 1.5 h / 170 - 180 °C 2: trichlorophosphate / 2 h / Reflux 3: N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) / dichloromethane / 6.5 h / Reflux 4: potassium borohydride / tetrahydrofuran; water / 3 h / 65 °C 5: hydrogen bromide / isopropyl alcohol / 5 h / Reflux 6: magnesium; iodine / diethyl ether / 1.5 h / 45 °C / Inert atmosphere
Multi-step reaction with 6 steps 1: sodium hydroxide / methanol / 1.5 h / 170 - 180 °C 2: trichlorophosphate / 2 h / Reflux 3: 2,2'-azobis(isobutyronitrile); N-chloro-succinimide / tetrachloromethane / 4.5 h / 20 °C 4: lithium borohydride / methanol / 5 h / 60 °C 5: hydrogenchloride / water; isopropyl alcohol / 4 h / Reflux 6: magnesium; iodine / tetrahydrofuran / 1.5 h / 65 °C
  • 14
  • 2-(4-ethylphenoxy)nicotinic acid [ No CAS ]
  • [ 52549-17-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: trichlorophosphate / 2 h / Reflux 2: N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) / dichloromethane / 6.5 h / Reflux 3: potassium borohydride / tetrahydrofuran; water / 3 h / 65 °C 4: hydrogen bromide / isopropyl alcohol / 5 h / Reflux 5: magnesium; iodine / diethyl ether / 1.5 h / 45 °C / Inert atmosphere
Multi-step reaction with 5 steps 1: trichlorophosphate / 2 h / Reflux 2: 2,2'-azobis(isobutyronitrile); N-chloro-succinimide / tetrachloromethane / 4.5 h / 20 °C 3: lithium borohydride / methanol / 5 h / 60 °C 4: hydrogenchloride / water; isopropyl alcohol / 4 h / Reflux 5: magnesium; iodine / tetrahydrofuran / 1.5 h / 65 °C
  • 15
  • [ 53944-31-3 ]
  • [ 52549-17-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) / dichloromethane / 6.5 h / Reflux 2: potassium borohydride / tetrahydrofuran; water / 3 h / 65 °C 3: hydrogen bromide / isopropyl alcohol / 5 h / Reflux 4: magnesium; iodine / diethyl ether / 1.5 h / 45 °C / Inert atmosphere
Multi-step reaction with 4 steps 1: 2,2'-azobis(isobutyronitrile); N-chloro-succinimide / tetrachloromethane / 4.5 h / 20 °C 2: lithium borohydride / methanol / 5 h / 60 °C 3: hydrogenchloride / water; isopropyl alcohol / 4 h / Reflux 4: magnesium; iodine / tetrahydrofuran / 1.5 h / 65 °C
  • 16
  • 7-(1-bromoethyl)-5H-[1]-benzopyrano[2,3-b] pyridin-5-one [ No CAS ]
  • [ 52549-17-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: potassium borohydride / tetrahydrofuran; water / 3 h / 65 °C 2: hydrogen bromide / isopropyl alcohol / 5 h / Reflux 3: magnesium; iodine / diethyl ether / 1.5 h / 45 °C / Inert atmosphere
  • 17
  • 7-(1-bromoethyl)-5H-[1]-benzopyrano[2,3-b]pyridin-5-ol [ No CAS ]
  • [ 52549-17-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: hydrogen bromide / isopropyl alcohol / 5 h / Reflux 2: magnesium; iodine / diethyl ether / 1.5 h / 45 °C / Inert atmosphere
  • 18
  • [ 61848-62-2 ]
  • [ 52549-17-4 ]
  • C21H26ClN3O3Pt [ No CAS ]
YieldReaction ConditionsOperation in experiment
52% With sodium carbonate; silver nitrate In N,N-dimethyl-formamide at 20℃; for 24h; Darkness; 48 Cis-dichloro-1,2-cyclohexanediamine platinum (190 mg), AgNO 3 (43 mg), pranoprofen (127.6 mg) andNa2C03 (35.3mg) added to the round bottom flask, and then add 10ml DMF, dark at room temperature 24h. The precipitate was centrifuged to remove AgCl. After the filtrate was concentrated, 50 ml of ethyl acetate was added and the mixture was washed three times with 50 ml of 0.1 M Na2CO3 and washed with water three times. The ethyl acetate layer was collected and dried over anhydrous sodium sulfate overnight. filter, And the filtrate was separated by silica gel column chromatography using methanol: chloroform = 1: 9 as eluant. The yield of pranoprofen-cyclohexanediamine platinum complex was 52%. The structural formula was as shown in Formula 47
  • 19
  • [ 52549-17-4 ]
  • C15H12N2O [ No CAS ]
  • (R)-2-(5H-chromeno[2,3-b]pyridin-7-yl)propanenitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: dmap; dicyclohexyl-carbodiimide / dichloromethane / 18 h / 0 - 20 °C 2: tris[2-phenylpyridinato-C2,N]iridium(III); copper(I) bromide; (3aR,3a’R,8aS,8a’S)-2,2’-(cyclopropane-1,1-diyl)bis(3a,8a-dihydro-8H-indeno[1,2-d]-oxazole) / para-xylene; N,N-dimethyl-formamide / 24 h / 20 °C / Irradiation; Sealed tube; Inert atmosphere
  • 20
  • [ 524-38-9 ]
  • [ 52549-17-4 ]
  • C23H16N2O5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
68% With dmap; dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃; for 18h;
  • 21
  • [ 77-86-1 ]
  • [ 52549-17-4 ]
  • C15H13NO3*C4H11NO3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
78% In ethanol at 70℃; 1 Example 1. Preparation of Praprofene derivative I-1-1 1 g of RS-pranoprofen (S1) and 0.475 g of tromethamine (tris, S2) were dissolved in 25 ml of ethanol to 70 ° C to dissolve. After dissolving, the oil was evaporated to dryness under reduced pressure to give an oil. Add 5 ml of each of isopropyl alcohol and ethyl acetate to triturate the crystals to obtain 1.16 g of the compound I-1-1. The yield was 78%.
  • 22
  • [ 93125-46-3 ]
  • [ 52549-17-4 ]
  • S-pranoprofen-N-octyl-D-glucosamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
22% In isopropyl alcohol Reflux; 2 Example 2 Preparation of S-type pranoprofen I-2-1 10 g of RS-pranoprofen and 5.75 g of N- octyl -D- glucosamine were suspended in 100 ml of isopropanol and dissolved by heating under reflux. After dissolving, it was naturally cooled to room temperature to be crystallized, and filtered to obtain 8.6 g of crude S- pranoprofen - N- octyl -D- glucosamine salt. The obtained crude product was recrystallized twice with 60 ml of isopropyl alcohol to give 4.2 g of S- pranoprofen - N- octyl -D- glucosamine salt. The exquisite 4.2 g of S- pranoprofen - N- octyl -D- glucosamine salt was suspended in 40 ml of water, and 1.6 g of potassium carbonate was added and stirred for 0.5 hour, and the resolving agent N-n-octyl group was removed by filtration. D-glucosamine, the obtained filtrate was extracted with 20 ml of ethyl acetate to remove the residual resolving agent N- octyl -D- glucosamine once in the alkali water, and the obtained alkali water was stirred under magnetic stirring, and the pH was adjusted to 5-6 with glacial acetic acid. The solid was precipitated, and the mixture was further stirred for 10 minutes, and then filtered, and the obtained solid was washed once with 20 ml of water, and then filtered and dried to give 1.7 g of the crude compound I-2-1. The crude compound I-2-1 was recrystallized from 15 ml of anhydrous ethanol to give 1.1 g of compound I-2-1, chiral purity: 99.5%, yield 22%.
  • 23
  • 7-(1,1-dimethoxy-2-hydroxypropyl)-5H-[1]-chromeno[2,3-b]pyridine [ No CAS ]
  • [ 52549-17-4 ]
YieldReaction ConditionsOperation in experiment
61% Stage #1: 7-(1,1-dimethoxy-2-hydroxypropyl)-5H-[1]-chromeno[2,3-b]pyridine With thionyl chloride; triethylamine In dichloromethane at 0 - 20℃; for 3h; Stage #2: With hydrogenchloride In dichloromethane; water at 60℃; for 3h; 1.4; 2.4; 3.4; 1; 2 Step (4) Add 7-(1,1-dimethoxy-2-hydroxypropyl)-5H-[1]-benzopyran[2,3-b]pyridine (40 g, 0.13 mol) to dichloromethane (200 ml) After cooling to about 0 ° C, first add triethylamine (26 g), then slowly add dropwise thionyl chloride (23 g,0.19mol), temperature control ≤ 20 ° C, after the completion of the dropwise addition to room temperature reaction for 3h, spin dry reaction system, then add 20ml concentrated hydrochloric acid, warmed to 60 ° C reaction for 3h, then the reaction solution was added to 200ml ice water, add 10% The sodium hydroxide solution was adjusted to pH=11, and the system was washed twice with 100 ml of dichloromethane. The aqueous layer was adjusted to pH=5 with acetic acid, and a large amount of solid was precipitated, and then stirred at room temperature for 2 hr, and filtered to obtain crude pranoprofen. After adding 200 ml of ethanol, the mixture was heated to reflux and dissolved. After cooling to room temperature, an equal amount of water was added, and the solid was precipitated and stirred for 2 hours, and then filtered to obtain 20 g of a white solid, which was a pranoprofen product, yield 61%, purity 99.7%.
  • 24
  • [ 261-27-8 ]
  • [ 52549-17-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: aluminum (III) chloride / dichloromethane / 3 h / 0 - 10 °C 2.1: N-Bromosuccinimide / tetrachloromethane / 5 h / Reflux 3.1: potassium <i>tert</i>-butylate / 3 h / 20 °C 4.1: triethylamine; thionyl chloride / dichloromethane / 3 h / 0 - 20 °C 4.2: 3 h / 60 °C
  • 25
  • 7-(1-propionyl)-5H-[1]-chromeno[2,3-b]pyridine [ No CAS ]
  • [ 52549-17-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: N-Bromosuccinimide / tetrachloromethane / 5 h / Reflux 2.1: potassium <i>tert</i>-butylate / 3 h / 20 °C 3.1: triethylamine; thionyl chloride / dichloromethane / 3 h / 0 - 20 °C 3.2: 3 h / 60 °C
  • 26
  • 2-hydroxy-1H-benzo[f]isoindole-1,3(2H)-dione [ No CAS ]
  • [ 52549-17-4 ]
  • 1,3-dioxo-1,3-dihydro-2H-benzo[f]isoindol-2-yl 2-(5H-chromeno[2,3-b]pyridin-7-yl)propanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
56% With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 12h; Cooling with ice;
  • 27
  • [ 52549-17-4 ]
  • (R)-7-(4-phenylbut-3-yn-2-yl)-5H-chromeno[2,3-b]pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: dmap; dicyclohexyl-carbodiimide / dichloromethane / 12 h / 20 °C / Cooling with ice 2: copper(l) iodide; caesium carbonate; C55H70N3O2P / 72 h / 20 °C / Schlenk technique; Inert atmosphere; Irradiation
  • 28
  • ethyl 2-(4-((3-formylpyridin-2-yl)oxy)phenyl)propanoate [ No CAS ]
  • [ 52549-17-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: titanium tetrachloride / dichloromethane / 24 h / 20 °C 2: lithium hydroxide / tetrahydrofuran; water / 3 h / 20 °C
  • 29
  • ethyl 2-(5H-chromeno[2,3-b]pyridin-7-yl)propanoate [ No CAS ]
  • [ 52549-17-4 ]
YieldReaction ConditionsOperation in experiment
90% With lithium hydroxide In tetrahydrofuran; water at 20℃; for 3h;
  • 30
  • [ 36404-90-7 ]
  • [ 52549-17-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 100 °C 2: titanium tetrachloride / dichloromethane / 24 h / 20 °C 3: lithium hydroxide / tetrahydrofuran; water / 3 h / 20 °C
  • 31
  • [ 56355-15-8 ]
  • [ 52549-17-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 100 °C 2: titanium tetrachloride / dichloromethane / 24 h / 20 °C 3: lithium hydroxide / tetrahydrofuran; water / 3 h / 20 °C
  • 32
  • [ 52549-17-4 ]
  • 4,4-difluorobutyl 2-(5H-chromeno[2,3-b]pyridin-7-yl)propanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: dmap; dicyclohexyl-carbodiimide / dichloromethane / 20 °C 2.1: copper(l) iodide; cesium fluoride / N,N-dimethyl-formamide / 6 h / 20 °C / Inert atmosphere; Glovebox; Schlenk technique 2.2: 6 h / 40 °C / Inert atmosphere; Glovebox; Schlenk technique
Multi-step reaction with 2 steps 1: dmap; dicyclohexyl-carbodiimide / dichloromethane / 20 °C 2: bis(dibenzylideneacetone)-palladium(0); 1,1'-bis-(diphenylphosphino)ferrocene; copper(l) iodide; cesium fluoride / N,N-dimethyl-formamide / 6 h / 50 °C / Inert atmosphere; Glovebox; Schlenk technique
  • 33
  • [ 52549-17-4 ]
  • [ 627-18-9 ]
  • 3-bromopropyl 2-(5H-chromeno[2,3-b]pyridin-7-yl)propanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
48% With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃;
  • 34
  • [ 627-32-7 ]
  • [ 52549-17-4 ]
  • C18H18INO3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃;
  • 35
  • [ 19249-03-7 ]
  • [ 52549-17-4 ]
  • (ethane-1,2-diylbis(oxy))bis(ethane-2,1-diyl) bis(2-(5H-chromeno[2,3-b]pyridin-7-yl)propanoate) [ No CAS ]
YieldReaction ConditionsOperation in experiment
38% With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 10h; II.18 (ethane-l,2-diylbis(oxy))bis(ethane-2,l-diyl) bis(2-(5H-chromeno[2,3-b]pyridin-7-yl)propanoate) (Pranoprofen-TEG-Pranoprofen, Compound 17) [00278] To a solution of pranoprofen (1.00 g, 3.93 mmol, 2.00 eq) in DMF (20.0 mL) was added K2CO3 (543 mg, 3.93 mmol, 2.0 eq) and triethylene glycol di(p-toluenesulfonate) (0.90 g, 1.96 mmol, 1.00 eq). The mixture was stirred at 80 °C for 10 h. The reaction mixture was poured into water (150 mL) and extracted with ethyl acetate (3 x 20 mL). The combined organic phase was washed with water (3 x 50.0 mL), dried with anhydrous Na2S04, filtered and concentrated in vacuo to give the crude product which was purified by column chromatography (Si02, Petroleum ether: Ethyl acetate = 5:1 to 1:1, TLC, Petroleum ether: Ethyl acetate = 0:1, the product Rf= 0.5) to give compound 5 (543 mg, 38%) as a colorless oil. HPLC retention time (Method 4): 37.1 min; 1H NMR (400 MHz, MeOD) d (ppm) 8.17 (dd, J = 4.80, 1.69 Hz, 2H), 7.53 (d, J = 7.20 Hz, 2H), 7.14- 7.19 (m, 2H), 7.08-7.14 (m, 4H), 7.03 (dd, J = 7.20, 4.88 Hz, 2H), 4.17-4.26 (m, 4H), 4.08 (s, 4H), 3.71 (q, J = 7.20 Hz, 2H), 3.61 (t, J = 4.80 Hz, 4H), 3.50 (s, 4H), 1.64 (s, 4H), 1.50 (s, 3H), 1.48 (s, 3H) LCMS m/z: [M + H]+ Calcd for C36H37N2O8625.2; Found 625.3.
  • 36
  • [ 52549-17-4 ]
  • [ 52549-44-7 ]
YieldReaction ConditionsOperation in experiment
55% With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 0 - 20℃; for 5h;
0.92 g With sodium perborate; glacial acetic acid at 50℃; for 3h; 1.1-1.3; 2.1-2.3; 3.1-3.3 (1) Dissolve 2.55 g of Pranoprofen crude drug in 20 mL of acetic acid solution, heat it to 50°C, add 3.0 g of sodium perborate in 5 times for more than 1 hour, and continue the heat preservation reaction for 2 hours after the addition is complete; (2) At the end of the reaction, vacuum concentration to remove acetic acid, add 20 mL of water, adjust PH=2 with sulfuric acid solution, extract 5 times with 10 mL of dichloromethane, combine the dichloromethane washings, and concentrate in vacuo; (3) Purify the concentrated product in step (2) with a silica gel column with a diameter of 1 cm and a height of 10 cm, eluting with dichloromethane, and concentrating the dichloromethane to obtain 0.92 g of the target compound, namely compound A3, with a purity of 97.73 %.
  • 37
  • [ 52549-17-4 ]
  • [ 52549-19-6 ]
YieldReaction ConditionsOperation in experiment
With dihydrogen peroxide In ethanol for 24h; Reflux; 1 Example 1 Add 10 g of (RS)-2-(10H-9-oxa-1-azaanthracene-6-yl)propionic acid (1) into a 500 ml reaction flask,Add 150 ml of ethanol and stir to dissolve the materials,Then add 50 ml of hydrogen peroxide, heat to reflux and react for 24 hours,Cool down to 010, add water and ethyl acetate,Continue to stir at room temperature for 0.5 hours, stand still, separate the liquids, save the organic phase,The organic phase was concentrated to dryness to obtain compound 2 concentrate,Used directly in the next reaction.
  • 38
  • [ 52549-17-4 ]
  • 2-(5H-chromeno[2,3-b]pyridin-7-yl)propan-1-ol [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% With borane-THF In tetrahydrofuran at 0 - 20℃; for 24h; Inert atmosphere;
  • 39
  • [ 52549-17-4 ]
  • pranoprofen [ No CAS ]
  • pranoprofen [ No CAS ]
YieldReaction ConditionsOperation in experiment
With CHIRALPAK IG In hexane; isopropanol at 25℃; Resolution of racemate;
  • 40
  • [ 52549-44-7 ]
  • [ 52549-17-4 ]
YieldReaction ConditionsOperation in experiment
With lithium hydroxide monohydrate In aq. phosphate buffer; dimethyl sulfoxide Radiolysis; Inert atmosphere;
  • 41
  • [ 52549-17-4 ]
  • [ 2829922-47-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: Reflux 1.2: 2 h / 60 °C / Cooling with ice 2.1: sodium hydride / tetrahydrofuran / 1 h / Inert atmosphere; Cooling with ice 2.2: 3 h / 20 °C
Multi-step reaction with 2 steps 1.1: Reflux 1.2: 2 h / 60 °C / Cooling with ice 2.1: sodium hydride / tetrahydrofuran / 1 h / Inert atmosphere; Cooling with ice 2.2: 3 h / 20 °C
  • 42
  • [ 3886-70-2 ]
  • [ 52549-17-4 ]
  • [ 103813-85-0 ]
YieldReaction ConditionsOperation in experiment
14.2% Stage #1: (R)-1-(1-Naphthyl)ethylamine; 2-(5h-[1]benzopyrano[2,3-b]pyridin-7-yl)propionic acid Reflux; Stage #2: With hydrogenchloride In water at 60℃; for 2h; Cooling with ice; 1.1; 1.2 Embodiment 1: the preparation of S(+)-pranoprofen Step 1: Preparation of Compound 1 Take pranoprofen (255.27g, 1.0mol) and add it to ethanol (4.0L),Heated to reflux, completely dissolved during heating,To this was slowly added a solution of R(-)-naphthylethylamine (188.36 g, 1.1 mol) in ethanol (1.0 L),A white solid was precipitated during the dropwise addition,Continue to reflux for 3.0h after the dropwise addition,Cooled to room temperature, filtered, and the obtained filter cake was rinsed with ethanol (200 mL×2),The obtained solid was dried by blowing at 45° C. for 12.0 h to obtain a crude product of compound 1 (335.70 g) with a yield of 78.7%. The obtained crude compound 1 (335.00 g) was added to a mixed solvent of acetone and ethanol (12:1, V/V, 3.5 L),Heat to reflux, continue to reflux for 2.0h after complete dissolution,Cool and crystallize to room temperature, filter,Rinse with the above mixed solvent of acetone and ethanol (200mL×2),The obtained filter cake was air-dried at 45 °C for 12.0 h to obtain compound 1.This operation was repeated 5 times to collect the obtained solid to obtain compound 1 refined product (79.90g),Purification yield: 23.9%. Overall yield: 18.8%.Step 2: Preparation of S(+)-pranoprofenCompound 1 refined product (79.00 g, 0.185 mol) was added to water (0.6 L),The pH was adjusted to about 3.0 with concentrated hydrochloric acid under ice bath conditions.Heated to 60 to de-salt for 2.0h,After cooling to room temperature, dichloromethane was added for extraction (1.0L×3),The combined organic phases were washed with saturated brine (1.0L×2),After drying over anhydrous sodium sulfate, it was concentrated, and the residue was purified by recrystallization from ethanol to obtain a solid.Blow dry at 45°C for 12.0h to obtain pure S(+)-pranoprofen (35.74g),Yield: 75.6%. Overall yield: 14.2% (based on pranoprofen). Purity: 99.7%.
Stage #1: (R)-1-(1-Naphthyl)ethylamine; 2-(5h-[1]benzopyrano[2,3-b]pyridin-7-yl)propionic acid In ethanol Reflux; Stage #2: With hydrogenchloride In water at 60℃; Cooling with ice; 1 Embodiment one: the separation of S-(+)-pranoprofen isomers in pranoprofen Get 510.50g (2.0mol) (RS)-pranoprofen () and join in 8.0L ethanol, heat to reflux, dissolve completely in the heating process, slowly add R (-)-naphthylethylamine (376.74g , 2.2mol) of ethanol (2.0L) solution, a white solid precipitated during the dropwise addition, and continued to reflux for 3.0h after the dropwise addition, cooled to room temperature, filtered, and the obtained filter cake was rinsed with ethanol (500mL×3), and the obtained The solid was air-dried at 45°C for 12.0 h to obtain 673.50 g of intermediate II crude product.Add 670.00 g of the obtained intermediate II crude product into 7.5 L of acetone and ethanol mixed solvent (12:1, V/V), heat to reflux, continue to reflux for 2.0 h after complete dissolution, cool and crystallize to room temperature, filter, and use The above-mentioned mixed solvent of acetone and ethanol was rinsed (500 mL×2), and the resulting filter cake was air-dried at 45° C. for 12.0 h to obtain intermediate II. This operation was repeated 3 times to obtain 162.08 g of intermediate II refined product by collecting the obtained solid. Yield: 19%.Add 160.00 g of intermediate II refined product to 1.2 L of water, adjust the pH to about 3.0 with concentrated hydrochloric acid under ice bath conditions, heat to 60 ° C to desalt for 2.0 h, add dichloromethane to extract after cooling to room temperature (1.4 L × 4), the combined organic phases were washed with saturated brine (2.4L×2), dried over anhydrous sodium sulfate, concentrated, and purified by ethanol recrystallization to obtain a solid, which was air-dried at 45°C for 12.0h to obtain 76.58g of pure product . Yield: 15% (calculated as pranoprofen). Chiral purity: 99.5%.
  • 43
  • [ 7677-24-9 ]
  • [ 52549-17-4 ]
  • [ 56653-86-2 ]
YieldReaction ConditionsOperation in experiment
81% With [2,2]bipyridinyl; copper acetylacetonate; tetrabutyl-ammonium chloride; platinum; cerium triflate In 2,2,2-trifluoroethanol; 1,2-dichloro-ethane; acetonitrile at 20 - 33℃; Schlenk technique; Inert atmosphere; Sealed tube; Irradiation; Electrochemical reaction; Electrolysis; Optical yield = 80 percent ee; enantioselective reaction;
  • 44
  • [ 7677-24-9 ]
  • [ 52549-17-4 ]
  • [ 161597-56-4 ]
YieldReaction ConditionsOperation in experiment
81% With copper acetylacetonate; tetrabutyl-ammonium chloride; C19H28N2O6; platinum; cerium triflate In 2,2,2-trifluoroethanol; 1,2-dichloro-ethane; acetonitrile at 20 - 33℃; Schlenk technique; Inert atmosphere; Sealed tube; Irradiation; Electrochemical reaction; Electrolysis; Optical yield = 80 percent ee; enantioselective reaction;
  • 45
  • [ 4521-28-2 ]
  • [ 52549-17-4 ]
  • [ 2878521-67-4 ]
YieldReaction ConditionsOperation in experiment
36 % Stage #1: 4-(4-Methoxyphenyl)butyric acid; 2-(5h-[1]benzopyrano[2,3-b]pyridin-7-yl)propionic acid With (1,2-dimethoxyethane)dichloronickel(II); di-<i>tert</i>-butyl dicarbonate; 4CzIPN; potassium carbonate; 4,4'-di-tert-butyl-2,2'-bipyridine In 1,2-dimethoxyethane at 20℃; Inert atmosphere; Stage #2: In 1,2-dimethoxyethane at 33℃; Inert atmosphere;
  • 46
  • [ 145986-74-9 ]
  • [ 52549-17-4 ]
YieldReaction ConditionsOperation in experiment
Ca. 83.8 % With sodium hydroxide In methanol; water at 40 - 45℃; Add compound IV-A (20.0g, 1 equiv.), hydrochloric acid (24.8g, 3.5 equiv.), isopropanol (240ml) into a 250ml reaction flask, stir to dissolve and heat up to 80°C-85°C for reflux reaction for 2h, 55°C Concentration under reduced pressure until no distillate was obtained to obtain a foamy oil (24 g).After cooling to room temperature, add methanol (10ml), stir to dissolve, add sodium hydroxide solution prepared by sodium hydroxide (11.2g, 4equiv.), purified water (40ml), and keep it at 40°C-45°C for 2h.Transfer to a 500ml beaker, add purified water (300ml), then extract the aqueous phase 4 times with ethyl acetate (100ml), separate the aqueous phase and adjust the pH to 3-4 with 10% dilute hydrochloric acid, and gradually precipitate a white powdery solid.Filter and rinse the filter cake with purified water and cold methanol in turn.Vacuum drying at 40°C gave 15.0 g of crude pranoprofen, with a yield of about 83.8% and a purity of 98.53%.
With water; sodium hydroxide In methanol at 20℃; Inert atmosphere; 1-5; 1-2 Example 1 Compound 1 (50g, 0.17mol) was added to a three-necked flask, and then 500mL of dichloromethane was added. After it was completely dissolved, pyridine (32g, 0.40mol) was added, and trifluoromethanesulfonic anhydride (57g, 0.20mol) was added dropwise under nitrogen protection. React at a temperature of 0-10°C for 3 hours, add water to wash and separate the liquid, concentrate the organic phase under reduced pressure, add methanol to the oil200mL and sodium hydroxide (20.0g, 0.51mol) water 50mL solution, react at room temperature under nitrogen protection for 1h, add water 450mL, and wash twice with dichloromethane 500mL successively, add acetic acid to the water phase to adjust the pH to 4~5, there is a large amount of The solid was precipitated, filtered, and dried to obtain 32.2 g of refined pranoprofen crude product, and 32.9 g of refined pranoprofen refined product was obtained by recrystallization from ethanol, with a total yield of 76% and a purity of 99.96% (0.01% was detected as olefin impurity A).
  • 47
  • [ 70-70-2 ]
  • [ 52549-17-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1.1: copper(l) iodide; sodium carbonate / N,N-dimethyl-formamide / 4 h / 75 - 115 °C 2.1: sulfuric acid / 15 min / 0 - 10 °C 2.2: 0 - 20 °C 3.1: thionyl chloride / N,N-dimethyl-formamide; dichloromethane / 1 h / 15 - 25 °C 4.1: aluminum (III) chloride / dichloromethane / -10 - 25 °C 5.1: sodium tetrahydroborate; acetic acid / dichloromethane; methanol / -5 - 30 °C / pH 5.5 - 6.5 6.1: hydrogenchloride / isopropyl alcohol / 2 h / 80 - 85 °C 7.1: sodium hydroxide / water; methanol / 2 h / 40 - 45 °C
Multi-step reaction with 7 steps 1.1: copper(l) iodide; sodium carbonate / N,N-dimethyl-formamide / 4 h / 75 - 135 °C 2.1: sulfuric acid / 15 min / 0 - 10 °C 2.2: 0 - 20 °C 3.1: thionyl chloride / N,N-dimethyl-formamide; dichloromethane / 1 h / 15 - 25 °C 4.1: aluminum (III) chloride / dichloromethane / -10 - 25 °C 5.1: sodium tetrahydroborate; acetic acid / dichloromethane; methanol / -5 - 30 °C / pH 5.5 - 6.5 6.1: hydrogenchloride / isopropyl alcohol / 2 h / 80 - 85 °C 7.1: sodium hydroxide / water; methanol / 2 h / 40 - 45 °C
Multi-step reaction with 7 steps 1.1: copper(l) iodide; sodium carbonate / N,N-dimethyl-formamide / 5 h / 75 - 115 °C 2.1: sulfuric acid / 15 min / 0 - 10 °C 2.2: 0 - 20 °C 3.1: thionyl chloride / N,N-dimethyl-formamide; dichloromethane / 1 h / 15 - 25 °C 4.1: aluminum (III) chloride / dichloromethane / -10 - 25 °C 5.1: sodium tetrahydroborate; acetic acid / dichloromethane; methanol / -5 - 30 °C / pH 5.5 - 6.5 6.1: hydrogenchloride / isopropyl alcohol / 2 h / 80 - 85 °C 7.1: sodium hydroxide / water; methanol / 2 h / 40 - 45 °C
  • 48
  • [ 143436-36-6 ]
  • [ 64-19-7 ]
  • [ 52549-17-4 ]
YieldReaction ConditionsOperation in experiment
53.0% Stage #1: 7-(1,1-dimethoxy-2-hydroxypropyl)-5H-[1]-chromeno[2,3-b]pyridine With sulfuryl dichloride; benzyltrimethylammonium chloride; triethylamine In dichloromethane at 0 - 20℃; Stage #2: acetic acid With hydrogenchloride In dichloromethane; water at 60℃; 1.2-1.3; 2.2-2.3; 1; 2; 3 2) Add the compound shown in 10g formula B and 110g dichloromethane in reaction flask,Cool to 0°C,Then add 12g triethylamine and 6g trimethylbenzyl ammonium chloride,Add dropwise 90g sulfuryl chloride solution (solvent is dichloromethane,The mass fraction of sulfonyl chloride is 10%), after the dropwise addition, react at room temperature for 18h, spin the solvent, then add 30g glacial acetic acid and 12g concentrated hydrochloric acid (mass concentration is 38%), react at 60°C for 3h, after the reaction ends The reaction solution was added to 100 ml of ice water, and then the pH value of the solution was adjusted to 11 with a mass fraction of 8% sodium hydroxide solution. The reaction system was washed with dichloromethane, and the water layer was collected, and the pH value of the water layer was adjusted to 5 with glacial acetic acid. A large amount of solids are separated out and filtered to obtain the crude product of pranoprofen;3) the pranoprofen crude product and ethanol aqueous solution that step 2) is obtained are mixed (the mass ratio of pranoprofen crude product and ethanol aqueous solution is 1:7, and the mass concentration of ethanol aqueous solution is 45%), heat and stir under 60 to make It dissolves, and the solution obtained after dissolving is divided into two parts (respectively denoted as the first solution and the second solution, the volume ratio of the first solution and the second solution is 20:1), the first solution is heated to make it reflux, The second solution is placed in an ultrasonic device and cooled to 30°C at room temperature, and the part of the solution is ultrasonically treated while cooling. The ultrasonic power is 150W. After the part of the solution is cooled to 30°C, it is added to the first solution, and then the first solution is cooled to crystallization, cooled to 20 ° C, the crystallization time is 5h, filtered, the filter cake is washed with water, and vacuum-dried at 80 ° C for 3 hours to obtain the pranoprofen (that is, the compound of formula C) , the yield is 53.0%, the HPLC purity is 99.88%, and the maximum simplex is 0.05%.
  • 49
  • [ CAS Unavailable ]
  • [ 52549-17-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
69.5 % In methanol at 25 - 30℃; 1.2-1.4; 2.2-2.4; 3.2-3.4; 4.2-4.4 (2) After the above reaction is completed, continue to add dropwise the methanol solution of pranoprofen (methanol solution is prepared by dissolving 8.3 g pranoprofen in 58 ml methanol) and control the temperature at 25 ° C ~ 30 ° C, and the drop will be completed within 30 min , after the dropwise addition is completed, keep the reaction at 25°C~30°C for 2h;(3) Concentrate and recover methanol under reduced pressure below 50°C. After recovering methanol, add 10% dilute hydrochloric acid dropwise at a temperature of 10°C~15°C to adjust the pH to 3~5, continue crystallization for 2 hours, and filter 10 mL of ethanol to wash the filter cake , the filter cake is dried under reduced pressure below 40°C;(4) Use a chromatographic column with a diameter of 3 cm, fill with 78 g of silica gel, rinse with dichloromethane methanol solution (V dichloromethane: V methanol = 2:1), rinse evenly, add the above-mentioned dried filter cake, and add the material Finally, 13 g of anhydrous sodium sulfate was laid on top, and eluted with dichloromethane methanol solution (V dichloromethane: V methanol = 2:1), and the first eluate was collected. After the first eluate was collected, Concentrate under reduced pressure below 40°C to dryness, beat 50 mL petroleum ether methanol solution (45 mL petroleum ether; 5 mL methanol) for 1 hour, filter, and dry the filter cake under reduced pressure at 40°C to obtain the target product of this paperHydroxide-(E)-2-[1-[3-(10H-9-oxa-1-azanthracene-6-yl)-2,3-dimethoxyallyl]-10H-9- Sodium oxa-1-azanthracene-1-cation-6-yl]propionate, the purity is 98.7%, and the yield is 69.5%.The compound II is 1-(5H-[1]benzopyran[2,3-b]pyridin-7-yl)-1,1-dimethoxypropane-2-sodium acetate.
  • 50
  • [ 7677-24-9 ]
  • [ 52549-17-4 ]
  • [ CAS Unavailable ]
  • [ 161597-56-4 ]
YieldReaction ConditionsOperation in experiment
83 % ee With copper acetylacetonate; (3aR,3'aR,8aS,8'aS)-2,2'-cyclopropylidenebis-[3a,8a]-dihydro-8H-indeno-[1,2-d]oxazole; potassium hydrogenphosphate trihydrate; iodosobenzene In acetone at 30℃; Inert atmosphere; Schlenk technique; Overall yield = 52 percent; Overall yield = 24.7 mg; enantioselective reaction;
  • 51
  • [ 873-76-7 ]
  • [ 52549-17-4 ]
  • [ 2940988-68-9 ]
YieldReaction ConditionsOperation in experiment
48% With dipotassium hydrogenphosphate; iron(III) trifluoromethanesulfonate In dichloromethane at 20℃; Inert atmosphere; Sealed tube; Irradiation; General Procedure B General procedure: An oven-dried 6-mL vial equipped with a stir bar is brought into a nitrogen-filled glovebox andcharged with Fe(OTf)3 (0.453 g, 3.0 equiv, 0.9 mmol), K2HPO4 (0.261 g, 5.0 equiv, 1.5 mmol), thealcohol nucleophile (3.0 equiv, 0.9 mmol), the carboxylic acid (1.0 equiv, 0.3 mmol), andmethylene chloride (3.0 mL, 0.10 M). The vial is sealed with a screwcap bearing a teflon septum,removed from the glovebox, and placed on a stir plate. The vial is irradiated at 427 nm with two40 W Kessil Lamp PR160 lamps at a distance of 10 cm with stirring at 800 rpm. A fan is used tomaintain the vial at room temperature. After 24 h, the crude reaction mixture is diluted with 1.5mL EtOAc and absorbed directly on diatomaceous earth (Celite). The product is purified by flashchromatography on silica gel.
  • 52
  • [ 3886-70-2 ]
  • [ 52549-17-4 ]
  • [ 2829922-50-9 ]
YieldReaction ConditionsOperation in experiment
67.9 % In ethanol Reflux; 1.1 Step 1: Preparation of compound S(+)-pranoprofen-Z1 Take Pranoprofen (25.5g, 100.0mmol)Added into ethanol (400mL),heated to reflux,slowly add to itR(-)-Naphthylethylamine (18.8g, 110mmol)ethanol (100mL) solution,During the dropwise addition, a white solid precipitated out,After the dropwise addition, continue to reflux for 3.0h,cooled to room temperature,Filter, and the resulting filter cake is rinsed with ethanol,Dry to obtain compound S (+)-pranoprofen-Z1 crude product (37.0g),Crude product yield: 86.8%.The obtained S(+)-pranoprofen-Z1 crude product is recrystallized with a mixed solvent (400mL) of acetone and ethanol, and crystallized at room temperature,filtered, rinsed, dried,The compound S(+)-pranoprofen-Z1 refined product (25.1 g) was obtained, and the refined yield: 67.9%.
  • 53
  • [ CAS Unavailable ]
  • [ 52549-17-4 ]
  • [ 2920686-17-3 ]
YieldReaction ConditionsOperation in experiment
Stage #1: 2-(5h-[1]benzopyrano[2,3-b]pyridin-7-yl)propionic acid With thionyl chloride In dichloromethane at 0 - 20℃; Inert atmosphere; Stage #2: acetaldehyde In dichloromethane at 0 - 20℃; 21.1 Step 1: Preparation of compound PLF67-XX1001 Under nitrogen protection, pranoprofen (2.0g, 7.8mmol)Added into dichloromethane (20mL), cooled to 0°C,Thionyl chloride (1.12 g, 9.4 mmol) was added slowly,After the addition was complete, the mixture was stirred at room temperature for 2 hours.The system was concentrated to dryness,The residue was concentrated several times with dichloromethane to remove excess thionyl chloride,Dichloromethane (10 mL) was added to the residue,Slowly added to dissolved aluminum chloride (0.63g, 4.7mmol)In dichloromethane solution (20mL),After joining,Stir at room temperature for 20 minutes.The system was cooled to 0°C,Acetaldehyde (0.4 g, 9.1 mmol) was added dropwise over 10 minutes.The reaction mixture was stirred at room temperature for 1 hour,The system was gradually added to a vigorously stirred ice-water slurry.Extracted 3 times with dichloromethane,Combine the organic phases,Washed twice with ice water,Separate the organic phase,dried over anhydrous sodium sulfate,No further processing is required,Concentrate to dryness and use directly in the next step.
  • 54
  • [ 2920685-95-4 ]
  • [ 52549-17-4 ]
  • [ 2920686-09-3 ]
YieldReaction ConditionsOperation in experiment
47.3 % With tetrabutylammomium bromide; sodium hydroxide In dichloromethane at 20℃; 15 Example 15: Synthesis of compound PLF67-XX04 Add dichloromethane (50mL) in reaction bottle,Then add pranoprofen (2.55g, 10mmol) successively,Tetrabutylammonium bromide (0.48g, 1.5mmol)and dissolved sodium hydroxide (2.0g, 50mmol)Aqueous solution (10mL),The above heterogeneous solution was then stirred for 15 minutes.Then slowly add dissolved compound ZJT2 (2.9g, 15mmol)dichloromethane solution (50mL),After the addition was complete, the mixture was stirred vigorously at room temperature for 8 hours.Then add the above systemdichloromethane (20mL) diluted,wash with water,Separate the organic phase,dried over anhydrous sodium sulfate,filter, concentrate,The residue was purified by silica gel column,Compound PLF67-XX04 (1.95g) was obtained,Yield 47.3%
  • 55
  • [ 2920685-94-3 ]
  • [ 52549-17-4 ]
  • [ 2920686-03-7 ]
YieldReaction ConditionsOperation in experiment
45.7 % With N-iodo-succinimide In tetrahydrofuran at 20℃; Inert atmosphere; 10 Embodiment 10: the synthesis of compound PLF67-XX01 In an argon atmosphere,Add tetrahydrofuran (250mL),Compound ZJT1 (2.12g, 12mmol),While stirring, slowly addN-iodosuccinimide (2.08g, 12mmol)and Pranoprofen (2.55g, 10mmol).After the addition was complete, the reaction was stirred at room temperature for 2 h,Filtration, the filtrate was concentrated under reduced pressure,The residue was added dichloromethane,Sodium thiosulfate,washed with saturated sodium bicarbonate and saturated brine,Separate the organic phase,dried over anhydrous sodium sulfate,filtered, concentrated, and the residue was purified by silica gel column,Obtain compound PLF67-XX01 (1.75g),Yield 45.7%.
  • 56
  • [ 56-87-1 ]
  • [ 52549-17-4 ]
  • [ 114672-62-7 ]
YieldReaction ConditionsOperation in experiment
65 % In ethanol; water Reflux; 8 Embodiment 8: Preparation of (RS)-pranoprofen-L-lysine salt (reference substance 1) Take (RS)-pranoprofen (2.55g, 10.0mmol) and add it to 200mL of absolute ethanol, add L-lysine (1.62g, 11.0mmol) to it, heat to reflux and dissolve completely, and continue to reflux for 5.0h , cooled and crystallized, a white solid precipitated out, filtered after cooling down to room temperature, the obtained filter cake was rinsed with absolute ethanol (5.0mL×2), and the obtained solid was air-dried at 45°C for 12.0h to obtain 2.61g of the product Reference Substance 1 . Yield: 65%. Purity: 98.6%.
Same Skeleton Products
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