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Chemical Structure| 90-45-9
Chemical Structure| 90-45-9
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Product Details of [ 90-45-9 ]

CAS No. :90-45-9 MDL No. :MFCD00037839
Formula : C13H10N2 Boiling Point : -
Linear Structure Formula :- InChI Key :XJGFWWJLMVZSIG-UHFFFAOYSA-N
M.W : 194.23 Pubchem ID :7019
Synonyms :
Aminacrine

Safety of [ 90-45-9 ]

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

Application In Synthesis of [ 90-45-9 ]

* 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 [ 90-45-9 ]

[ 90-45-9 ] Synthesis Path-Downstream   1~38

  • 1
  • [ 90-45-9 ]
  • [ 79-04-9 ]
  • [ 100954-63-0 ]
YieldReaction ConditionsOperation in experiment
With acetone
With triethylamine In tetrahydrofuran at 0℃; for 4h; 3.1.1. General Procedure for the Synthesis of N-(9-Acridinyl)-2-Chloroacetamide Derivatives (2) General procedure: Chloroacetyl chloride (30 mmol, 2.4 mL) in THF (10 mL) was added dropwise while stirring to amixture of 9-aminoacridine (1; 20 mmol, 3.9 g) and triethylamine (40 mmol, 5.6 mL) in THF (50 mL)at 0-5 °C and stirred for 4 h. The solvent was evaporated under reduced pressure. The residue waswashed with water to remove triethylamine hydrochloride, before being dried and crystallized fromethano
  • 2
  • [ 1207-69-8 ]
  • [ 110166-26-2 ]
YieldReaction ConditionsOperation in experiment
93% With ammonium carbonate; In phenol; at 70 - 120℃; for 2h; Intermediate compound 1 was dissolved in phenol in a round bottom flask at 70 C, 1 mmol of <strong>[1207-69-8]9-chloroacridine</strong> was added, 2 mmol of ammonium carbonate was added, and the temperature was rapidly raised to 120 C for 2 h, and the reaction was completed and poured into 10 wt. It was filtered, washed with 10 wt% NaHH and water to give a pale yellow solid with strong blue fluorescence. 9-Amino Acridine Intermediate Compound 2, yield 93%.
93% With ammonium carbonate; In phenol; at 70 - 120℃; for 2h; Intermediate compound I was dissolved in phenol in a round bottom flask at 70 C with 1 mmol of <strong>[1207-69-8]9-chloroacridine</strong> and 2 mmol of ammonium carbonate was added.Rapidly warm to 120 C for 2 h,Pour into 10% NaOH until the reaction is complete.Filtered and washed with 10% NaOH and water to give a pale yellow solid.Has strong blue fluorescence.9-aminoacridine intermediate compound II,The yield was 93%.
93% With ammonium carbonate; In phenol; at 70 - 120℃; for 2h; The intermediate compound I (<strong>[1207-69-8]9-chloroacridine</strong>) was dissolved in phenol in a round bottom flask at 70 C, 1 mmol of <strong>[1207-69-8]9-chloroacridine</strong> was added, 2 mmol of ammonium carbonate was added, and the temperature was rapidly raised to 120 C for 2 h. After the reaction was completed, it was poured into 10% NaOH, filtered, and washed with 10% NaOH and water to give a pale yellow solid, 9-amino acridine intermediate compound II with strong blue fluorescence, yield 93%.
9.5 g With sodium tetrahydroborate; sodium azide; tetrabutylammomium bromide; In dichloromethane; at 20℃; for 3h; Intermediate () 10. 68 g (0.05 mol) was dissolved in 500 ml of methylene chloride, and the mass ratio of 1:10A mixed solution of sodium azide and distilled water, and 17.5 g of tetrabutylammonium bromide were placed in a stoppered flat-bottomed flask at room temperatureUnder stirring lh,Then 3 g of sodium borohydride was added and the mixture was stirred for 2 h. The layers were separated and the aqueous phase was extracted twice with methylene chloride.Machine phase, drying, concentration, purification intermediates (f) 9. 5g;
With ammonium carbonate; phenol; at 70 - 120℃; for 2h; Add 3 mmol of acridinone to a double-necked flask equipped with a condenser and a stir bar, Charge N2, Add 6mL POCl3 in a nitrogen atmosphere, Reflux at 105 for 3h, After the reaction is completed, cool to room temperature, slowly drop the reaction solution into ice water with stirring, add the mixture of concentrated ammonia and chloroform to the above liquid, separate the chloroform layer, dry (anhydrous magnesium sulfate), and filter to obtain A pale yellow liquid was purified through the column with (V ethyl acetate: V petroleum ether = 1: 3) to obtain white needle crystals of <strong>[1207-69-8]9-chloroacridine</strong>. In a 100 mL round-bottom flask, dissolve 1 mmol of <strong>[1207-69-8]9-chloroacridine</strong> in phenol at 70 C, add 2 mmol of ammonium carbonate, quickly warm to 120 C for 2 h, and pour into 10% NaOH at the end of the reaction, filter, Wash with 10% NaOH and water to obtain a pale yellow compound II (2- (4-bromophenyl) benzo [d] [1,3] selenazole) solid;

  • 3
  • [ 110166-26-2 ]
  • [ 321-64-2 ]
  • [ 127842-43-7 ]
  • [ 114990-34-0 ]
  • [ 13415-07-1 ]
YieldReaction ConditionsOperation in experiment
1: 60% 2: 5.2% 3: 4.3% With hydrogen In ethanol at 80℃; for 2h; other pressure, other reaction temperature and times, other catalysts; Yield given. Further byproducts given;
  • 4
  • [ 110166-26-2 ]
  • [ 321-64-2 ]
  • [ 127842-42-6 ]
  • [ 114990-34-0 ]
  • [ 13415-07-1 ]
YieldReaction ConditionsOperation in experiment
1: 60% 2: 5.2% 3: 4.3% With hydrogen In ethanol at 80℃; for 2h; other pressure, other reaction temperature and times, other catalysts; Yield given. Further byproducts given;
  • 5
  • [ 90-45-9 ]
  • [ 577-19-5 ]
  • [ 80260-77-1 ]
YieldReaction ConditionsOperation in experiment
73% With caesium carbonate In N,N-dimethyl-formamide at 90℃; for 12h;
73% With caesium carbonate In N,N-dimethyl-formamide at 90℃; for 12h; 6 Example 6. Synthesis of N-(2-nitrophenyI)acridin-9-amine - Compound 109-Aminoacridine (0.194 g, 1 mmol), 1 -bromo-2-nitrobenzene (0.201 g, 1 mmol) and Cs2C03 (0.161 g, 0.5 mmol) were heated in 5 mL of dry DMF at 90°C for 12 h. While heating, the color of the reaction mixture changed to dark red. After completion of the reaction (TLC monitoring in DCM) the reaction mixture was cooled and poured into water. The precipitate was collected by filtration, washed several times with water and dried to give orange crude solid. The crude product was purified by flash chromatography on silica gel 60 (DCM) to yield pure orange Compound 10 (0.23 g, 73% yield): HRMS (DI, m/z) calculated for C19H,3N302 (MH+) 316.325, found 316.321; NMR (δ, ppm, CDC13): 9.32. (bs, 1, NH), 8.24 (d, 2H, J=6.8 Hz), 8.01-7.88 (m, 3H), 7.71-7.53 (m, 4H), 7.33 (t, 1H, J=7.0 Hz), 6.62 (d, 1H, J=7.0 Hz). 13C NMR (δ, ppm, CDC13): 165.2, 154.3, 147.7, 144.1, 133.4, 130.0, 129.7, 128.7, 127.2, 125.6, 124.7, 122.3, 120.5.
  • 6
  • [ 90-45-9 ]
  • [ 86-81-7 ]
  • [ 908078-62-6 ]
YieldReaction ConditionsOperation in experiment
68% With sodium cyanoborohydride; acetic acid In methanol at 20℃; for 3h;
68% Stage #1: aminacrine; 3,4,5-trimethoxy-benzaldehyde With methanol; acetic acid at 20℃; for 0.25h; Stage #2: With sodium cyanoborohydride In methanol at 20℃; for 3h; 4 Example 4. Synthesis of N-(3,4,5-trimethoxybenzyl)acridin-9-amine - Compound 69-Aminoacridine (0.194 g, 1 mmol) and 3,4,5-trimethoxybenzaldehyde (0.196 g, 1 mmol) were added to 5 mL of MeOH/AcOH (99: 1) and stirred at room temperature until starting material dissolved (15 min). Then, NaCNBH3 (0.09 g, 1.5 mmol) in small portions was added with stirring. After additional stirring for 3 h at room temperature, the solvent was evaporated and the residue was purified by flash chromatography on silica gel 60 (5% MeOH in ethyl acetate) to yield pure yellow product. 0.25g of pure product as yellow solid (68% yield): HRMS (DI, m/z) calculated for C22H23N203 (MH+) 375.163, found 375.161; NMR (δ, ppm, DMSO-i¾: 8.45 (d, 2H, J=7.00 Hz), 7.88 (d, 2H, J=7.00 Hz), 7.72 (t, 2H, d, 2H, J=7.00 Hz), 7.55 (t, 2H, J=7.00 Hz), 6.68 (s, 2H), 4.57 (s, 2H, -NH-CH2-), 3.76 (s, 3H), 3.74 (s, 6H). 13C NMR (δ, ppm, DMSO-<¾: 162.2, 141.0, 131.5, 129.0, 128.5, 126.2, 125.7, 125.5, 124.6, 124.3, 123.4, 122.9, 122.4, 121.7, 1 14.5, 66.1, 60.7, 58.3.
  • 7
  • [ 110166-26-2 ]
  • [ 97-51-8 ]
  • [ 1211776-26-9 ]
YieldReaction ConditionsOperation in experiment
87% With sodium cyanoborohydride; acetic acid In methanol at 20℃; for 3h;
87% Stage #1: aminacrine; 5-Nitrosalicylaldehyde With methanol; acetic acid at 20℃; for 0.25h; Stage #2: With sodium cyanoborohydride In methanol at 20℃; for 3h; 3 Example 3. Synthesis of 2-((acridin-9-ylamino)methyl)-4-nitrophenol - Compound 39-Aminoacridine (0.194 g, 1 mmol) and 2-hydroxy-5-nitrobenzaldehyde (0.152 g, 1 mmol) were added to 5 mL of MeOH/AcOH (99: 1) and stirred at room temperature until starting material dissolved (15 min). Then, NaCNBH3 (0.09 g, 1.5 mmol) in small portions was added with stirring. After additional stirring for 3 h at room temperature, the solvent was evaporated and the residue was taken into acetone. The precipitate was filtered in vacuum, washed with acetone and dried to give 0.29 g of pure product as yellow solid (87% yield), FT-IR (vmax, KBr): 3400-3150(bs), 1620, 1350, 1190 cm"1; HRMS (DI, m/z) calcd for C2oHi5N303 (MH+) 346.1 1 1 found 346.1 15; NMR (DMSO- d6): δ 8.42 (d, 2H, J=7.00 Hz), 7.95 (dd, 1H, J=7.00, 1.80 Hz), 7.84-7.80 (m, 3H), 7.69- 7.65 (m, 2H) ), 7.34-7.31 (m, 2H), 6.66 (d, 1H, J=6.80 Hz), 4.68 (s, 2H, -NH-CH2-), 13C NMR (δ, ppm, DMSO-i¾: 163.8, 137.0, 130.5, 130.0, 129.5. 126.3, 125.9, 125.5, 124.8, 124.1, 123.6, 123.0, 122.1, 121.6, 112.5, 64.1.
  • 8
  • [ 110166-26-2 ]
  • [ 119-67-5 ]
  • [ 1211776-24-7 ]
YieldReaction ConditionsOperation in experiment
92% With sodium cyanoborohydride; acetic acid In methanol at 20℃; for 3h;
92% Stage #1: aminacrine; o-carboxybenzaldehyde With methanol; acetic acid at 20℃; for 0.25h; Stage #2: With sodium cyanoborohydride In methanol at 20℃; for 3h; 2 Example 2. Synthesis of 2-(acridin-9-ylaminomethyl)benzoic acid - Compound 19-Aminoacridine (0.194 g, 1 mmol) and 2-formylbenzoic acid (0.15 g, 1 mmol) were added to 5 mL of MeOH/AcOH (99: 1) and stirred at room temperature until starting material dissolved (15 min). Then, NaCNBH3 (0.09 g, 1.5 mmol) in small portions was added with stirring. After additional stirring for 3 h at room temperature, the solvent was evaporated and the residue was taken into acetone. The precipitate was filtered in vacuum, washed with acetone and dried to give 0.3 g of pure product as yellow solid (0.3 g, 92% yield): FT-TR (vmax, KBr): 3500-3180 (bs), 1700 (C=0), 1640, 1290 cm"1; HRMS (DI, m/z) calculated for C21H16N202 (MH+) 329.364, found 329.363; 1H NMR (δ, ppm, CDC13): 8.50 (d, 2H, J=7.00 Hz), 7.92 (d, 2H, J=7.00 Hz), 7.77 (d, 1H, J=6.80 Hz), 7.68- 7.65 (m, 2H), 7.39-7.35 (m, 3H), 4.54 (s, 2H, -NH-CH2-); 13C NMR (δ, ppm, CDC13): 171.9 (C02H), 168.7, 152.7, 146.5, 141.5, 139.0, 131.5, 130.6, 130.1, 128.6, 128.2, 126.3, 125.5, 123.6, 122.1, 64.1.
  • 9
  • [ 110166-26-2 ]
  • [ 96-99-1 ]
  • [ 1211776-36-1 ]
YieldReaction ConditionsOperation in experiment
86% With caesium carbonate In N,N-dimethyl-formamide at 90℃; for 12h;
Stage #1: aminacrine; 4-chloro-3-nitrobenzoate With caesium carbonate In N,N-dimethyl-formamide at 90℃; for 12h; Stage #2: With hydrogenchloride In water; N,N-dimethyl-formamide 7 Example 7. Synthesis of 4-(acridin-9-ylamino)-3-nitrobenzoic acid - Compound 139-Aminoacridine (0.194 g, 1 mmol), 4-chloro-3-nitrobenzoic acid (0.20 g, 1 mmol) and Cs2C03 (0.161 g, 0.5 mmol) were heated in 5 mL of dry DMF at 90°C for 12 h. While heating, the color of the reaction mixture changed to dark red. After completion of the reaction (TLC monitoring in 10% MeOH/DCM) the reaction mixture was cooled and poured into water. The pH was adjusted to 6 by careful addition of 0.1 N HC1. The precipitate was collected by filtration, washed several times with water and dried to give pure Compound 13 as orange crude solid (0.335 g, 86% yield): vmax (KBr): 3450- 3200(bs), 1705 (C=0), 1600, 1245 cm'1; HRMS (DI, m/z) calculated for C20H13N3O4 (MH+) 360.091, found 360.101 ; NMR (δ, ppm, DMSO-i 6): 8.56. (s, 1H), 8.30-8.27 (m, 3H), 8.00-7.90 (m, 3H), 7.66-7.58 (m, 3H), 7.17 (d, 1H, J=6.80 Hz); 13C NMR (<5, ppm, DMSO-< ): 173.0 (C02H), 164.2, 153.1, 148.2, 143.5, 132.4, 131.0, 128.9, 127.7, 127.0, 126.2, 125.6, 121.4, 120.5.
  • 10
  • [ 117-80-6 ]
  • [ 90-45-9 ]
  • [ 1296099-10-9 ]
YieldReaction ConditionsOperation in experiment
82% With caesium carbonate In N,N-dimethyl-formamide at 90℃; for 12h; 9.2 Example 9. Synthesis of 9-aminoacridine derivatives containing substituted quinone radicals [Compounds 34-41] via addition-elimination (AE) or SNAr reactionTwo one-pot reaction modes were employed: (i) addition-elimination reaction by refluxing in ethanol overnight, and (ii) SNAT reaction with Cs2C03 in DMF at 90°C for 12 h. The successful one pot synthesis of the end products resulted in moderate to good yields.9.1 General procedure for the synthesis via addition-elimination (AE) reaction:9-Aminoacridine (0.194 g, 1 mmol) and haloquinone compound (1 mmol) were refluxed in 15 mL of EtOH for overnight. While heating, the color of the reaction mixture in most cases changed to dark red or gray. After completion of the reaction (TLC monitoring in CH2C12) the mixture was cooled and evaporated to give a crude red or gray solid. The products were purified by flash column chromatography on silica gel 60 to yield corresponding products.9.2 General procedure for the synthesis via S^Ar reaction:9-Aminoacridine (0.194 g, 1 mmol), haloaryl or haloquinone compound (1 mmol), and Cs2C03 (0.161 g, 0.5 mmol) were heated in 5 mL of dry DMF at 90°C for 12 h. While heating, the color of the reaction mixture in most cases changed to dark red. After completion of the reaction (TLC monitoring in 5%MeOH in CH2C12) the mixture was cooled and poured into water. The resulting precipitate was collected by filtration, washed several times with water, and dried to give a crude red or orange solid. The products were purified by flash column chromatography on silica gel 60 to yield the corresponding products.The following compounds were obtained, most of them in moderate to good yields after chromatography:Compound 34: 2-(acridin-9-ylamino)-3-ethoxy,5,6-dichlorobenzoquinone, by reaction with tetrachlorobenzoquinone in ethanol under reflux overnight (yield - 57%);Compound 35: 2-(acridin-9-ylamino)-3-bromo-5-ethoxy-benzoquinone, by reaction with tetrabromobenzoquinone in ethanol under reflux overnight (yield - 3%);Compound 36: 2-(acridin-9-ylamino)-3,6-dibromo-5-ethoxycyclohexa-2,5-diene- 1,4-dione, by reaction with tetrabromobenzoquinone in ethanol under reflux overnight; Compound 37: 2-(acridin-9-ylamino)-3-chloro-5-ethoxycyclohexa-2,5-diene-l,4- dione;Compound 38: 2-(acridin-9-ylamino)-3,5,6-tribromobenzoquinone, by reaction with tetrabromobenzoquinone and Cs2C03 in dry DMF at 90°C for 12 h. (yield - 79%);Compound 39: 2-(acridin-9-ylamino)-3-chloronaphthoquinone, by reaction with 2,3-dichloronaphthoquinone and Cs2C03 in dry DMF at 90°C for 12 h. (yield - 82%);Compound 40: 2-(acridin-9-ylamino)-3-chloro-6,7-dimethylnaphthoquinone, by reaction with 2,3-dichloro-6,7-dimethylnaphthoquinone and Cs2C03 in dry DMF at 90°C for 12 h. (yield - 88%); andCompound 41 : 2-(acridin-9-ylamino)-3-ethoxy-5,8-dihydroxy-naphthoquinone, by reaction with 2,3-dichloro-5,8-dihydroxy-naphthoquinone in ethanol under reflux overnight (yield - 86%);To demonstrate the synthetic potential of AE reaction with 9-aminoacridine, we employed two classes of representative quinones: halobenzoquinones and halonaphthoquinones yielding respective bifunctional quinono-9-aminoacridine derivatives 26-31 under mild conditions. During the examination, we noticed that different reaction conditions led to different products. When an equimolar amount of tetrachlorobenzoquinone was reacted with 9-aminoacridine in refluxing ethanol overnight, the product 2-(acridin-9-ylamino)-3,6-dichloro-5-ethoxycyclohexa-2,5-diene-l ,4-dione- (Compound 34) was obtained, after chromatography (silica gel, CHC13), in 57% yield. Interestingly, this molecule possesses one ethoxyl group in E position to 9-amino of acridine as a result of additional AE reaction with EtOH (chemical structure was characterized by d-NOE, HMBC, HMQC experiments). The same conditions used for the reaction of analogous tetrabromobenzoquinone led to the formation of single reduced E product 2-(acridin-9-ylamino)-3-bromo-5-ethoxy-benzoquinone (Compound 35) in very low yield (3%). The MS spectrum (C21H] 5BrN203, m/z (M") 421.22 (92%), 424.28 (100%) clearly showed the presence of only one bromine atom and NMR confirmed the presence of one quinone hydrogen (5.93s). On the other hand, using aprotic conditions (1 eq of Cs2C03 in DMF at 90°C for 12 h) only 2,3,5,6- tetrabromobenzoquinone underwent classical S AT reaction leading to 2-(acridin-9- ylamino)-3,5,6-tribromobenzoquinone (Compound 38) in 79% yield after purification. Other tetrahaloquinones, 2,3,5,6-tetrachloro- and 2,3,5,6-tetrafluorobenzoquinone, under these conditions afforded unidentified mixtures. Moving forward, we decided to switch at that point to chlorobenzoquinone reactants for obtaining more massive benzoquinone moiety on 9-aminoacridine by AE reaction. Benzoquinone, for example, can bear additional amino, hydroxyl and methoxy groups that, together with quinonic the ketone group, are able to enhance biologically important chelating properties, leading to formation of DNA damaging reactive species.2,3-Dichloro or 2,3-dichloro-6,7-dimethyl- naphthalene- 1,4-dione was reacted with 9-aminoacridine in boiling ethanol affording gray crude products (39 and 40, respectively). Simple work up followed by evaporation of solvent and subsequent purification by flash chromatography (silica gel, EtOAc : PE, 1 :2) gave corresponding products 39 and 40 in 82% and 88% yields, respectively. The existence of CI atom was confirmed by MS spectra clearly showing 3:1 of chlorine isotope ratio (C23Hi ClN202, m/z (MH+) 385.213 (98%), 387.324 (31%) for Compound 39, C25H18C1N202, m/z (MH+): 412.311 (92%), 414.298(27%) for Compound 40).Encouraged by this result, we reacted the biologically more interesting 2,3- dichloro-5,8-dihydroxynaphthalene- 1,4-dione with 9-aminoacridine in boiling ethanol to afford a reddish crude Compound 41 that did not require any further purification and was analyzed as is. Surprisingly, the spectral analysis identified Compound 41 as a result of double EA reaction, once by 9-aminoacridine and secondly by EtOH, similarly to quinone derivatives 34 and 35 but oppositely to benzoquinone analogs 39 and 40. The structural conformation was supported by an observed high-field shift in the 1H NMR spectrum for the nonsymmetrical phenolic protons at δ 11.82 and δ 12.33 and typical low-field shift for ethoxy group (δ 4.66, q, J=6.5 Hz for 2H and δ 1.37, t, J=6.5 Hz for 3H).
82% In ethanol Reflux;
  • 11
  • [ 90-45-9 ]
  • [ 488-48-2 ]
  • [ 1296099-08-5 ]
YieldReaction ConditionsOperation in experiment
79% With caesium carbonate In N,N-dimethyl-formamide at 90℃; for 12h; 9.2 9.2 General procedure for the synthesis via S^Ar reaction:9-Aminoacridine (0.194 g, 1 mmol), haloaryl or haloquinone compound (1 mmol), and Cs2C03 (0.161 g, 0.5 mmol) were heated in 5 mL of dry DMF at 90°C for 12 h. While heating, the color of the reaction mixture in most cases changed to dark red. After completion of the reaction (TLC monitoring in 5%MeOH in CH2C12) the mixture was cooled and poured into water. The resulting precipitate was collected by filtration, washed several times with water, and dried to give a crude red or orange solid. The products were purified by flash column chromatography on silica gel 60 to yield the corresponding productsCompound 38: 2-(acridin-9-ylamino)-3,5,6-tribromobenzoquinone, by reaction with tetrabromobenzoquinone and Cs2C03 in dry DMF at 90°C for 12 h. (yield - 79%);
79% With caesium carbonate In N,N-dimethyl-formamide at 90℃; for 12h;
  • 12
  • [ 90-45-9 ]
  • [ CAS Unavailable ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate In N,N-dimethyl-formamide at 20℃; for 24h; 12 Example 12. Solid Phase Synthesis of 9-anilinoacridine derivatives by SNArThe solid phase synthesis of 2-nitro-4-carboxy- and 2-nitro-4-carboxamido-9- anilino derivatives is depicted in Scheme 7 herein. First, a solution of 3-nitro-4- fluorobenzoic acid in the solvents described in Scheme 7 was loaded on the Rink Amide MBHA or Cl-Trt resin and the resulting bound carboxamido or ester was reacted with 9- aminoacridine under S AT conditions. After cleavage, from the Cl-Trt Resin the 2-nitro-4- carboxy-9-anilinoacridine (Compound 13) was obtained in high yield (93%) and purity (94%) and from the Rink Amide MBHA Resin the 2-nitro-4-carboxamido-9- anilinoacridine (Compound 14) was obtained in high yield (96%) and purity (93%).
  • 13
  • [ CAS Unavailable ]
  • [ 90-45-9 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate In N,N-dimethyl-formamide at 20℃; for 24h; 12 Example 12. Solid Phase Synthesis of 9-anilinoacridine derivatives by SNArThe solid phase synthesis of 2-nitro-4-carboxy- and 2-nitro-4-carboxamido-9- anilino derivatives is depicted in Scheme 7 herein. First, a solution of 3-nitro-4- fluorobenzoic acid in the solvents described in Scheme 7 was loaded on the Rink Amide MBHA or Cl-Trt resin and the resulting bound carboxamido or ester was reacted with 9- aminoacridine under S AT conditions. After cleavage, from the Cl-Trt Resin the 2-nitro-4- carboxy-9-anilinoacridine (Compound 13) was obtained in high yield (93%) and purity (94%) and from the Rink Amide MBHA Resin the 2-nitro-4-carboxamido-9- anilinoacridine (Compound 14) was obtained in high yield (96%) and purity (93%).
  • 14
  • [ 90-45-9 ]
  • [ 61103-10-4 ]
  • [ 1296099-12-1 ]
YieldReaction ConditionsOperation in experiment
88% With caesium carbonate In N,N-dimethyl-formamide at 90℃; for 12h; 9.2 Example 9. Synthesis of 9-aminoacridine derivatives containing substituted quinone radicals [Compounds 34-41] via addition-elimination (AE) or SNAr reactionTwo one-pot reaction modes were employed: (i) addition-elimination reaction by refluxing in ethanol overnight, and (ii) SNAT reaction with Cs2C03 in DMF at 90°C for 12 h. The successful one pot synthesis of the end products resulted in moderate to good yields.9.1 General procedure for the synthesis via addition-elimination (AE) reaction:9-Aminoacridine (0.194 g, 1 mmol) and haloquinone compound (1 mmol) were refluxed in 15 mL of EtOH for overnight. While heating, the color of the reaction mixture in most cases changed to dark red or gray. After completion of the reaction (TLC monitoring in CH2C12) the mixture was cooled and evaporated to give a crude red or gray solid. The products were purified by flash column chromatography on silica gel 60 to yield corresponding products.9.2 General procedure for the synthesis via S^Ar reaction:9-Aminoacridine (0.194 g, 1 mmol), haloaryl or haloquinone compound (1 mmol), and Cs2C03 (0.161 g, 0.5 mmol) were heated in 5 mL of dry DMF at 90°C for 12 h. While heating, the color of the reaction mixture in most cases changed to dark red. After completion of the reaction (TLC monitoring in 5%MeOH in CH2C12) the mixture was cooled and poured into water. The resulting precipitate was collected by filtration, washed several times with water, and dried to give a crude red or orange solid. The products were purified by flash column chromatography on silica gel 60 to yield the corresponding products.The following compounds were obtained, most of them in moderate to good yields after chromatography:Compound 34: 2-(acridin-9-ylamino)-3-ethoxy,5,6-dichlorobenzoquinone, by reaction with tetrachlorobenzoquinone in ethanol under reflux overnight (yield - 57%);Compound 35: 2-(acridin-9-ylamino)-3-bromo-5-ethoxy-benzoquinone, by reaction with tetrabromobenzoquinone in ethanol under reflux overnight (yield - 3%);Compound 36: 2-(acridin-9-ylamino)-3,6-dibromo-5-ethoxycyclohexa-2,5-diene- 1,4-dione, by reaction with tetrabromobenzoquinone in ethanol under reflux overnight; Compound 37: 2-(acridin-9-ylamino)-3-chloro-5-ethoxycyclohexa-2,5-diene-l,4- dione;Compound 38: 2-(acridin-9-ylamino)-3,5,6-tribromobenzoquinone, by reaction with tetrabromobenzoquinone and Cs2C03 in dry DMF at 90°C for 12 h. (yield - 79%);Compound 39: 2-(acridin-9-ylamino)-3-chloronaphthoquinone, by reaction with 2,3-dichloronaphthoquinone and Cs2C03 in dry DMF at 90°C for 12 h. (yield - 82%);Compound 40: 2-(acridin-9-ylamino)-3-chloro-6,7-dimethylnaphthoquinone, by reaction with 2,3-dichloro-6,7-dimethylnaphthoquinone and Cs2C03 in dry DMF at 90°C for 12 h. (yield - 88%); andCompound 41 : 2-(acridin-9-ylamino)-3-ethoxy-5,8-dihydroxy-naphthoquinone, by reaction with 2,3-dichloro-5,8-dihydroxy-naphthoquinone in ethanol under reflux overnight (yield - 86%);To demonstrate the synthetic potential of AE reaction with 9-aminoacridine, we employed two classes of representative quinones: halobenzoquinones and halonaphthoquinones yielding respective bifunctional quinono-9-aminoacridine derivatives 26-31 under mild conditions. During the examination, we noticed that different reaction conditions led to different products. When an equimolar amount of tetrachlorobenzoquinone was reacted with 9-aminoacridine in refluxing ethanol overnight, the product 2-(acridin-9-ylamino)-3,6-dichloro-5-ethoxycyclohexa-2,5-diene-l ,4-dione- (Compound 34) was obtained, after chromatography (silica gel, CHC13), in 57% yield. Interestingly, this molecule possesses one ethoxyl group in E position to 9-amino of acridine as a result of additional AE reaction with EtOH (chemical structure was characterized by d-NOE, HMBC, HMQC experiments). The same conditions used for the reaction of analogous tetrabromobenzoquinone led to the formation of single reduced E product 2-(acridin-9-ylamino)-3-bromo-5-ethoxy-benzoquinone (Compound 35) in very low yield (3%). The MS spectrum (C21H] 5BrN203, m/z (M") 421.22 (92%), 424.28 (100%) clearly showed the presence of only one bromine atom and NMR confirmed the presence of one quinone hydrogen (5.93s). On the other hand, using aprotic conditions (1 eq of Cs2C03 in DMF at 90°C for 12 h) only 2,3,5,6- tetrabromobenzoquinone underwent classical S AT reaction leading to 2-(acridin-9- ylamino)-3,5,6-tribromobenzoquinone (Compound 38) in 79% yield after purification. Other tetrahaloquinones, 2,3,5,6-tetrachloro- and 2,3,5,6-tetrafluorobenzoquinone, under these conditions afforded unidentified mixtures. Moving forward, we decided to switch at that point to chlorobenzoquinone reactants for obtaining more massive benzoquinone moiety on 9-aminoacridine by AE reaction. Benzoquinone, for example, can bear additional amino, hydroxyl and methoxy groups that, together with quinonic the ketone group, are able to enhance biologically important chelating properties, leading to formation of DNA damaging reactive species.2,3-Dichloro or 2,3-dichloro-6,7-dimethyl- naphthalene- 1,4-dione was reacted with 9-aminoacridine in boiling ethanol affording gray crude products (39 and 40, respectively). Simple work up followed by evaporation of solvent and subsequent purification by flash chromatography (silica gel, EtOAc : PE, 1 :2) gave corresponding products 39 and 40 in 82% and 88% yields, respectively. The existence of CI atom was confirmed by MS spectra clearly showing 3:1 of chlorine isotope ratio (C23Hi ClN202, m/z (MH+) 385.213 (98%), 387.324 (31%) for Compound 39, C25H18C1N202, m/z (MH+): 412.311 (92%), 414.298(27%) for Compound 40).Encouraged by this result, we reacted the biologically more interesting 2,3- dichloro-5,8-dihydroxynaphthalene- 1,4-dione with 9-aminoacridine in boiling ethanol to afford a reddish crude Compound 41 that did not require any further purification and was analyzed as is. Surprisingly, the spectral analysis identified Compound 41 as a result of double EA reaction, once by 9-aminoacridine and secondly by EtOH, similarly to quinone derivatives 34 and 35 but oppositely to benzoquinone analogs 39 and 40. The structural conformation was supported by an observed high-field shift in the 1H NMR spectrum for the nonsymmetrical phenolic protons at δ 11.82 and δ 12.33 and typical low-field shift for ethoxy group (δ 4.66, q, J=6.5 Hz for 2H and δ 1.37, t, J=6.5 Hz for 3H).
88% In ethanol Reflux;
  • 15
  • [ 90-45-9 ]
  • [ CAS Unavailable ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate In N,N-dimethyl-formamide at 20℃; for 24h; 13 The solid phase synthesis of other amino acid derivatives Compounds 43-46 is depicted in Scheme 9 below.Thus it can be seen that high yields and high purity were obtained for derivatives obtained using protected glycine, serine, lysine and arginine as the amino acids.
  • 16
  • [ 90-45-9 ]
  • [ CAS Unavailable ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate In N,N-dimethyl-formamide at 20℃; for 24h; 13 The solid phase synthesis of other amino acid derivatives Compounds 43-46 is depicted in Scheme 9 below.Thus it can be seen that high yields and high purity were obtained for derivatives obtained using protected glycine, serine, lysine and arginine as the amino acids.
  • 17
  • [ 90-45-9 ]
  • [ CAS Unavailable ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate In N,N-dimethyl-formamide at 20℃; for 24h; 14 Example 14. Solid phase synthesis of bis-9-aniIinoacridine-MBP peptide conjugate 51The synthesis of the conjugate 51 is depicted in Scheme 10. Initially, the peptide MBP of SEQ ID NO: l was synthesized on a Rink amide MB HA, using solid phase peptide synthesis (SPPS), by attaching to the resin protected amino acids according to the sequence SEQ ID NO: l . Then, the protedted lysine residue Fmoc-Z-Lys(Fmoc) was reacted with 3-nitro-4-fluorobenzoic acid, followed by the aromatic nucleophilic substitution procedure with 9-aminoacridine. More particularly, 4.5 g of Rink amide methylbenzhydrylamine (MBHA) resin (0.68 mmol/g) was swollen for 2 h in N- methylpyrrolidone (NMP) in a reaction vessel equipped with a sintered glass bottom, and placed on a shaker. The Fmoc group was removed with 20% piperidine in NMP (twice for 30 min). After washing with NMP (five times for 2 min) and DCM (two times for 2 min), Fmoc removal was monitored using the ninhydrin Kaiser test. A coupling cycle was carried out with Fmoc-amino acids (3 eq.), bromo-tris pyrrolidino-phosphonium hexafluorophosphate (PyBrOP) (3 eq.), DIEA (6 eq.) in NMP for 2 h at room temperature. The resin was washed with NMP (five times for 2 min) and DCM (two times for 2 min). Reaction completion was monitored using the ninhydrin Kaiser test. Fmoc removal, washings and coupling of Fmoc-amino acids were performed as described above. Peptide elongation was performed by repeating the cycle described above. After the coupling of Fmoc-pAla-OH and subsequent Fmoc removal and washings as described above, coupling of the Fmoc-L-Lys(Fmoc)OH was performed with premixed amino acid acid (3^.6 eq.), PyBrOP (3^.6 eq.), and DIEA (6-9.2 eq.) in NMP. Reaction completion was monitored using the ninhydrin Kaiser test. Then, a preactivated solution of fluoronitrobenzoic acid (2.78 mmol acid, 2.78 mmol PyBoP, 7.34 mmol NMM in 10.5 mL DMF) was added to the resin and shaken for 40 min. Then the resin was washed with 2xDMF, 2xDCM (10 mL each) and the aromatic substitution procedure with 9- aminoacridine with 0.8 g Cs2C03 in 10 ml DMF was performed for 24 h. After washings with 2xH20, 2xDMF, 2xMeOH, 2xDCM and 2xDMF (7 mL each) the resin was transferred to a vial for cleavage and a cold solution of 2.5% H20/1.5% triisopropyl silane, 1% ethane dithiol in 95% TFA (5 mL) was added. After shaking for 1.5 h, the solution was collected and the resin was washed with cold TFA (2x1 mL each). After combining the TFA solutions, the solvent was evaporated first by N2 stream and then in vacuum to give an oily crude peptide. The peptide was precipitated by treating the concentrated solution with cold ether (35 ml). The ether was removed by centrifugation and the precipitant was washed three times by cold ether. After the usual work up (fast purification by solid-phase extraction pack RP-18, first washed with water and then extracted with acetonitrile, 8 mL each), the peptide was collected and dried and submitted to purification by semipreparative HPLC (0.1%TFA/H2O and CH3CN).
  • 18
  • [ 90-45-9 ]
  • [ CAS Unavailable ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate In N,N-dimethyl-formamide at 20℃; for 24h; 11 Example 10. Preparation of Compounds 42-50 containing amino acid residue by solid phase synthesis10.1 General procedure for solid phase synthesis on Cl-Trt resin:To 2-chlorotrityl resin (0.2 g, 0.28 mmol loading) in a reactor was added a solution of properly protected amino acid (0.26 mmol) in dry DMF (3.5 mL) and after addition of diisopropylethylamine (DIEA, 185 mL, 1.04 mmol) the reaction mixture was shaken for 1.5 h. After completion of the loading, dry MeOH (1.5 mL) was poured into the reactor and shaking continued for an additional 20 min. The solvent was filtered out and the following washings were sequentially performed: 2xDCM:MeOH:DIEA (17:2: 1), 2xDCM, 2xDMF, 2xDCM, 2xDCM:DMF (1 : 1) (3 mL each). The Fmoc protecting group was removed by reaction with 20% piperidine in N-methyl-2-pyrrolidone (NMP) (2x15 min, 5 mL each) and subsequent washing (2xDCM, 2xDMF, 5 mL each). Then, a preactivated solution of 3-nitro-4-fluorobenzoic acid (0.78 mmol acid, 0.78 mmol PyBoP, 2.34 mmol DIEA in 4.5 mL DMF) was added to the resin and shaken for 2 h. Then the resin was washed with 2x DMF, 2xDCM (3 mL each) and the aromatic substitution procedure of 9-aminoacridine with 0.5 g Cs2C03 in 3 ml DMF was performed for 24 h. After washings by 2xH20, 2xDMF, 2xMeOH, 2xDCM and 2xDMF (3 mL each) the resin was transferred to a vial for cleavage and a cold solution of 1% TFA in DCM (2 mL) was added. After shaking for 30 min, the solution was collected and the resin was washed several times with DCM (3 mL each). After combining the organic solutions, the solvent was evaporated first by N2 stream and then in vacuum to give after the usual work up (fast purification by solid-phase extraction pack RP-18, first washed with water and then extracted with acetonitrile, 5 mL each) the 9-anilinoacridine- amino acid conjugate with a free COOH group.10.2 General procedure for solid phase synthesis on Rink Amide MBHA resin:The procedure for the synthesis on Rink amide MBHA resin is identical to the synthesis on Cl-Trt resin except for the loading and the cleavage:Loading: The Fmoc protecting group from Rink amide was removed by reaction with 20% piperidine in NMP (2x15 min, 5 mL each) and subsequent washing (2xDCM, 2xDMF, 5 mL each). Then, a preactivated solution of 3-nitro-4-fluorobenzoic acid (0.78 mmol acid, 0.78 mmol PyBoP, 2.34 mmol DIEA in 4.5 mL DMF) was added to the resin and shaken for 2 h. Then the resin was washed with 2x DMF, 2xDCM (3 mL each).Cleavage: the resin was transferred to a vial for cleavage and a cold solution of 2.5% H20/2.5% triisopropyl silane in 95% TFA (2 mL) was added. After shaking for 1.5 h, the solution was collected and the resin was washed with cold TFA (2x1 mL each). After combining the TFA solutions, the solvent was evaporated first by N2 stream and then in vacuum to give after the usual work up (fast purification by solid-phase extraction pack RP-18, first washed with water and then extracted with acetonitrile, 5 mL each) the 9-anilinoacridine- amino acid conjugate with a CONH2 group.Example 11. Synthesis of 4-(acridin-9-ylamino)-N-(l-amino-5-guanidino-l- oxopentan-2-yl)-3-nitrobenzamide (Compound 45) by solid phase synthesisThe synthesis was performed on Rink Amide MBHA as described in Example 10 and depicted in Scheme 6. To the resin was added a solution of the protected arginine molecule Fmoc-(Z)Arg(Pbf)-OH. The resin-bound protected arginine was then reacted with 3-nitro-4-fluorobenzoic acid and after then with 9-aminoacridine and Cs2C03 in DMF for 24 h at room temperature. After cleavage of the resin, Compound 45 was obtained in good yield (97%) and 90% purity, and was characterized: as a yellowish powder (0.083 g, 97% yield). MS m/z 515.2 (MH+), 1 H NMR (300 MHz, DMSO-i¾): 8.80 (m,lH), 8.63 (m,lH), 8.92-8.88 (m, 2H), 8.50-8.35 (m, 4H), 7.8 (d, J = 8Hz, 2H), 7.60-7.45 (m, 4H), 7.14-6.95 (m, 3H), 4.21 (m, 1H), 3.26- 3.02 (m, 4H), 1.55 (m, 2H). Example 12. Solid Phase Synthesis of 9-anilinoacridine derivatives by SNArThe solid phase synthesis of 2-nitro-4-carboxy- and 2-nitro-4-carboxamido-9- anilino derivatives is depicted in Scheme 7 herein. First, a solution of 3-nitro-4- fluorobenzoic acid in the solvents described in Scheme 7 was loaded on the Rink Amide MBHA or Cl-Trt resin and the resulting bound carboxamido or ester was reacted with 9- aminoacridine under S AT conditions. After cleavage, from the Cl-Trt Resin the 2-nitro-4- carboxy-9-anilinoacridine (Compound 13) was obtained in high yield (93%) and purity (94%) and from the Rink Amide MBHA Resin the 2-nitro-4-carboxamido-9- anilinoacridine (Compound 14) was obtained in high yield (96%) and purity (93%).
  • 19
  • [ 90-45-9 ]
  • [ 53384-26-2 ]
  • [ 1446010-74-7 ]
YieldReaction ConditionsOperation in experiment
85% In 1,4-dioxane for 3h; Reflux; 5.4 Synthesis of disubstituted thiourea derivatives 5 and 6a,b General procedure: A solution of isothiocyanate 3 (0.01mol) in 30mL dioxane, 9-aminoacridine, 2-amino-N-(3-trifluoromethylphenyl)-benzamide or 2-amino-N-(4-ethoxyphenyl)-benzamide (0.01mol) was added. The reaction mixture was heated under reflux for 3h. The solution was concentrated under vacuum, left to cool. The solid product so formed was filtered off, washed with ethanol, dried well, and recrystallized from ethanol/dioxane.
  • 20
  • [ 134-50-9 ]
  • [ 90-45-9 ]
YieldReaction ConditionsOperation in experiment
100% With sodium hydroxide In water; ethyl acetate for 0.25h; 5.1 (1) 9-Aminoacridine (1) 9-Aminoacridine Aminoacridine hydrochloride (2g, 8.7 mmol) was added to a mixture of sodium hydroxide (0.7g, 17.4mmol) in water (100mL) and EtOAc (100mL) stirred for 15 min. The EtOAc layer was separated and the aqueous layer was washed with EtOAc (3x50mL). The organic fractions were combined and dried (Na2CO3), filtered and concentrated in vacuo to give an orange crystalline solid (1.7g, quantitative).
  • 21
  • [ 90-45-9 ]
  • [ 141-97-9 ]
  • [ 943415-89-2 ]
YieldReaction ConditionsOperation in experiment
84.16% at 120℃; for 3h; Synthesis of N-acridin-9-yl-3-oxo-butyramide, 3 A mixture of 9-aminoacridine 1 (0.02 mol) and ethyl acetoacetate 2 (0.02 mol) was refluxed on oil bath at 120°C for 3 hr to afford N-acridin-9-yl-3-oxo-butyranlide. Completion of the reaction was monitored with thin layer chromatography and the crude residue was recrystallized with absolute ethyl alcohol to get pure yellow product which was identified as an N-acridin-9-yl-3-oxo-butyramide 3, yield: 84.16%; m.p. 192°C.
for 0.0333333h; Microwave irradiation; Preparation of N-acridin-9-yl-3-oxo-butyramide 3 A mixture of 9-aminoacridine 1 (0.02 mol) and ethylacetoacetate 2 (0.02 mol) was irradiated under microwave condition for 2 min and cooled to room temp which afforded yellow residue. The solid was recrystallized from absolute ethanol.
  • 22
  • [ 15905-16-5 ]
  • [ 90-45-9 ]
  • [ 1817724-79-0 ]
YieldReaction ConditionsOperation in experiment
57% With water In methanol at 20℃; for 4h; 2.4. Synthesis of (H9a-acr)2(pydco)*2H2O (1) A methanolic solution of 9-aminoacridine (0.2 mmol, 40 mg)was added to an aqueous solution of pyridine-2,6-dicarboxylic acidN-oxide (0.1 mmol, 10 mg) (2:1 M ratio) and the mixture was stirredat room temperature for 4 h. Yellow crystals were obtained byslow evaporation of the reaction mixture at room temperatureafter 10 days (yield: 57%, m.p. 178 C). Elemental analysis: Anal.Calc. for C33H29N5O7: C, 65.23; H, 4.81; N, 11.53. Found: C, 64.93;H, 4.68; N, 11.41%. IR bands (KBr pellet, cm1): 3740.9, 3115.5,1692.6, 1633.8, 1588.4, 1486.1, 1357.8, 1270.8, 1209.5, 1161.3,1033.2, 960.1, 904.8, 846.8, 811.7, 757.9, 695, 655.7.
  • 23
  • [ 15905-16-5 ]
  • [ 90-45-9 ]
  • [ 7732-18-5 ]
  • [ CAS Unavailable ]
  • [ 1817724-83-6 ]
YieldReaction ConditionsOperation in experiment
45% In methanol at 20℃; for 4h; 2.5. Synthesis of {(H9a-acr)2[Cu(pydco)2(H2O)2]4H2O} (2) A methanolic solution of 9-aminoacridine (0.1 mmol, 20 mg)was added to an aqueous solution of pyridine-2,6-dicarboxylicacid-N-oxide (0.1 mmol, 20 mg) and copper(II) acetate monohydrate(0.05 mmol, 10 mg) and the mixture was stirred at roomtemperature for 4 h. The green precipitate formed during this timewas dried and redissolved in 10 mL of water. Green block crystalswere obtained after 2 days by slow evaporation of the solution atroom temperature (yield: 45%, m.p. 197.2 C). Elemental analysis:Anal. Calc. for C40H40CuN6O16: C, 51.40; H, 4.31; N, 9.22. Found:C, 51.92; H, 4.24; N, 9.82%. IR bands (KBr pellet, cm1): 3105.3, 3062.1, 1720, 1633, 1590, 1477.4, 1398.6, 1354.8, 1246.9, 1188.4,1077, 915.7, 855.7, 764.2, 706.2, 653.8.
  • 24
  • [ 15905-16-5 ]
  • [ 90-45-9 ]
  • [ 7732-18-5 ]
  • [ CAS Unavailable ]
  • [ 1817724-87-0 ]
YieldReaction ConditionsOperation in experiment
42% Stage #1: Pyridine-2,6-dicarboxylic acid N-oxide; aminacrine; water In methanol at 60 - 70℃; for 2h; Stage #2: nickel(II) acetate tetrahydrate In methanol at 60 - 70℃; for 3h; 2.6. Synthesis of {(H9a-acr)2[Ni(pydco)2(H2O)2]4H2O} (3) A methanolic solution of 9-aminoacridine (0.1 mmol, 20 mg)was added to an aqueous solution of pyridine-2,6-dicarboxylicacid-N-oxide (0.1 mmol, 20 mg) and the solution was stirred at60-70 C for 2 h. Then a solution of Ni(CH3COO)24H2O (0.05 mmol,0.0124 g), in deionized water/methanol (5 mL) was added dropwiseand the resulting reaction mixture was stirred for an additional3 h at the same temperature. Golden yellow crystals wereobtained by slow evaporation of the reaction mixture at room temperatureafter 1 month (yield: 42%, m.p. 198 C). Elemental analysis:Anal. Calc. for C40H40N6NiO16: C, 52.25; H, 4.38; N, 9.14. Found:C, 51.89; H, 4.25; N, 8.98%. IR (cm1, KBr): 3494.6, 3047.5, 1724.2,1634.9, 1591.8, 1480.5, 1396.4, 1359.7, 1245.6, 1168.3, 1077,844.9, 766.6, 665.9.
  • 25
  • [ 90-45-9 ]
  • [ CAS Unavailable ]
  • [ CAS Unavailable ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
55% Stage #1: aminacrine With 4-methyl-morpholine In N,N-dimethyl-formamide for 0.166667h; Stage #2: [Ru(4,4'-dicarboxy acid-2,2'-bipyridine)(2,2'-bipyridine)Cl2] In N,N-dimethyl-formamide for 24h; Reflux; Stage #3: ammonium hexafluorophosphate 2.3. cis-[Ru(dcbH2)(bpy)(9AA)Cl]2+ 0.034 g (0.17 mmol) of 9AA was dissolved in 10 mL of DMF followed by addition of 30 mL of N-methylmorpholine (NMM) under stirring. After 10 min, 0.100 g (0.17 mmol) of [Ru(dcbH2)(bpy)Cl2] was added, and the mixture was kept under stirring and reflux for 24 h. At the end of the reaction, the solid is filtered off and the solvent was removed from the filtrate by rotary-evaporator under vacuum. The residue was dissolved in a minimum amount of methanol and loaded on a P2 column. The desired complex was eluted with 20-80% of methanol-H2O containing 20 mM KCl as a dark red fraction, which was concentrated by rotary-evaporator under vacuum till near dryness. The thick slurry obtained was then precipitated by adding NH4PF6. The precipitate wasfiltered off, washed with acetone, and dried under vacuum. After then, the solid was recrystallized in methanol. Yield: 55%. Anal. calcd for C35H26N6O4ClRuP2F12: C, 41.17; H, 2.57; N, 8.23; found: C, 41.50; H,2.79; N, 8.77. HRMS calcd for C35H26N6O4ClRu: 731.1401 and [C35H26N6O4ClRu]2+ (base peak): 365.5366. Found: 731.0732 and 365.5365 (Fig. S1 in the Supporting Information). LM (methanol,103 mol L1) = 170 μS cm-1 mol-1. IR (KBr pallet, cm-1) 1718 (νCOOH), 1420 (δCH+ + δNH), 843 (νPF).
  • 26
  • [ 90-45-9 ]
  • [ 537-98-4 ]
  • [ 1900683-71-7 ]
YieldReaction ConditionsOperation in experiment
85% at 145℃; for 0.0833333h; Microwave irradiation; General procedure for synthesis of mono and bisamide derivatives of ferulic acid General procedure: (E)-3-(4-hydroxy-3-methoxyphenyl)acrylic acid (ferulic acid)and corresponding amines (IIa-IIo, IVa-IVg, VIa-VIg andVIIIa-VIIIe) were mixed together thoroughly in anequimolar ratio for mono-amide and 2:1 molar ratio for bisamidewithin a Petri dish. The reactionmixture was subjectedto microwave irradiation at 180-450 Watt for 3-7 min. Theprogress of the reactions was monitored by thin layer chromatography(TLC) on silica gel using ethyl acetate/methanol(4:1, 3:2 and 7:3) as solvent of elution. TLCs indicated theabsence of startingmaterials and confirmed the completion ofreaction and formation of products.The crude products thus soobtainedwere purified by crystallization and re-crystallizationin methanol to give the pure products (IIIa-IIIo, Va-Vg, VIIa-VIIg and IXa-IXe) in high yield.
  • 27
  • [ 260-94-6 ]
  • [ 57-13-6 ]
  • [ 90-45-9 ]
YieldReaction ConditionsOperation in experiment
78% Stage #1: urea With sodium hydride In dimethyl sulfoxide; mineral oil at 20℃; Inert atmosphere; Stage #2: acridine In dimethyl sulfoxide; mineral oil at 20℃; for 24h; Inert atmosphere; General procedure. To a solution of the corresponding urea (3mmol) in anhydrous dimethyl sulfoxide (5mL), sodium hydride (3mmol, based on active ingredient) was added at room temperature. When hydrogen bubbling ceased, acridine (0.5mmol) was added. The mixture was stirred vigorously at room temperature for 24h. Then water (30mL) was added and the precipitate was filtered off, washed with water and dried. Compounds 3, 7 and 10 were purified by recrystallization from the appropriate solvents (see ESI). Product 6 was additionally washed with hot water on the filter (∼70°C; 40mL) during isolation to remove excess starting materials and the dry product was recrystallized from a mixture of dichloromethane and petroleum-ether. Compound 5 was purified by silica gel flash chromatography, eluting with a 5:1 mixture of benzene-EtOAc (colorless fraction) and then with EtOAc (yellow fraction). The first fraction containing the starting materials was discarded; product 5 was obtained from the second fraction after solvent evaporation. Data for 9-aminoacridine (3): yellow solid (76mg, 78% upon use urea and 72mg, 74%, using phenyl urea); mp 232-233°C (EtOAc). Lit6b mp 233-234°C. 1H NMR (400MHz, DMSO-d6): δ 8.39 (2H, br d, J=8.4 Hz, H-1,8); 7.81 (2H, br d, J=8.5 Hz, H-4,5); 7.77 (2H, br s, NH2); 7.64 (2H, ddd, J=8.5Hz, J=8.0Hz, J=1.0 Hz, H-3,6); 7.31 (2H, ddd, J=8.4Hz, J=8.0Hz, J=1.0Hz, H-2,7). 13C NMR (100 MHz, DMSO-d6): δ 150.1; 148.8; 129.8; 128.7; 123.3; 121.5; 112.9. IR (thin film) 3342, 3181, 1649, 1613, 1562 cm-1. ESI-HRMS: calcd for C13H11N2 [M+H]+ 195.0917, found 195.0919.
  • 28
  • [ 260-94-6 ]
  • [ 64-10-8 ]
  • [ 110166-26-2 ]
YieldReaction ConditionsOperation in experiment
74% Stage #1: phenyl carbamate With sodium hydride In dimethyl sulfoxide; mineral oil at 20℃; Inert atmosphere; Stage #2: acridine In dimethyl sulfoxide; mineral oil at 20℃; for 24h; Inert atmosphere; General procedure. To a solution of the corresponding urea (3mmol) in anhydrous dimethyl sulfoxide (5mL), sodium hydride (3mmol, based on active ingredient) was added at room temperature. When hydrogen bubbling ceased, acridine (0.5mmol) was added. The mixture was stirred vigorously at room temperature for 24h. Then water (30mL) was added and the precipitate was filtered off, washed with water and dried. Compounds 3, 7 and 10 were purified by recrystallization from the appropriate solvents (see ESI). Product 6 was additionally washed with hot water on the filter (∼70°C; 40mL) during isolation to remove excess starting materials and the dry product was recrystallized from a mixture of dichloromethane and petroleum-ether. Compound 5 was purified by silica gel flash chromatography, eluting with a 5:1 mixture of benzene-EtOAc (colorless fraction) and then with EtOAc (yellow fraction). The first fraction containing the starting materials was discarded; product 5 was obtained from the second fraction after solvent evaporation. Data for 9-aminoacridine (3): yellow solid (76mg, 78% upon use urea and 72mg, 74%, using phenyl urea); mp 232-233°C (EtOAc). Lit6b mp 233-234°C. 1H NMR (400MHz, DMSO-d6): δ 8.39 (2H, br d, J=8.4 Hz, H-1,8); 7.81 (2H, br d, J=8.5 Hz, H-4,5); 7.77 (2H, br s, NH2); 7.64 (2H, ddd, J=8.5Hz, J=8.0Hz, J=1.0 Hz, H-3,6); 7.31 (2H, ddd, J=8.4Hz, J=8.0Hz, J=1.0Hz, H-2,7). 13C NMR (100 MHz, DMSO-d6): δ 150.1; 148.8; 129.8; 128.7; 123.3; 121.5; 112.9. IR (thin film) 3342, 3181, 1649, 1613, 1562 cm-1. ESI-HRMS: calcd for C13H11N2 [M+H]+ 195.0917, found 195.0919.
  • 29
  • [ 1972640-53-1 ]
  • [ 90-45-9 ]
YieldReaction ConditionsOperation in experiment
95% In 5,5-dimethyl-1,3-cyclohexadiene for 1h; Reflux; Conversion of 1-acridin-9-yl-3-tert-butyl-urea (5) into 9-aminoacridine (3). A solution of 1-acridin-9-yl-3-tert-butyl-urea (146.5 mg, 0.5 mmol) in xylene (7 mL)was refluxed within 1h. After cooling to room temperature the precipitate of 3 was filtered off, washed with petroleum-ether and dried. 9-aminoacridine (3) was obtained as yellow solid (92 mg, 95%); mp 232-233 oC (EtOAc).
  • 30
  • [ 110166-26-2 ]
  • [ 3407-93-0 ]
YieldReaction ConditionsOperation in experiment
Stage #1: aminacrine With hydrogenchloride; sodium nitrite In water at -5 - 0℃; for 1h; Stage #2: With hydrogenchloride; tin(ll) chloride In water General procedure for the synthesis of 9-hydrazinylacridine (1) General procedure: 9-aminoacridine was dissolved in concentrated hydrochloricacid (HCl) and cooled to about 0 C. Cooled solution of sodium nitrite in water (1.1 equivalent) was slowly added to the above maintaining temperature at about 0°C for about 1 h till the reaction was over. To the diazotized product, acidified stannous chloride was slowly added till completion of the reaction. The reduced product was then worked up with sodium hydroxide (NaOH) and extracted with ethyl acetate. The solvent was distilled under reduced pressure, and crude compound was crystallized to get pure 9-hydrazinylacridine.
  • 31
  • [ 90-45-9 ]
  • [ 1967815-29-7 ]
  • [ 1967815-53-7 ]
YieldReaction ConditionsOperation in experiment
66% With acetic acid In ethanol for 6h; Reflux; General procedure for synthesis of compounds 13-15 General procedure: A mixture of the chloropyridine derivative 2 (0.01 mol), aromatic and heteroamines, namely p-toluidine, 4-fluoroaniline, 9-aminoacridine or 2-aminothiazole (0.01 mol), in ethanol/acetic acid (30 mL) was heated under reflux for 6 h. The reaction mixture was concentrated and the obtained precipitate was filtered off and recrystallized from acetic acid or dioxane.
  • 32
  • [ 110166-26-2 ]
  • [ 499128-71-1 ]
  • C43H31N3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; for 0.166667h;Microwave irradiation; 4.76 g (0. Olmol) (g),Intermediate f (f) l 94 g (0.01 mol), Cs2C036. 52 g (0.02 mol),Pd (dppf) Cl2 0.17 g (0.0005 mol)In 15 g of 1,4-dioxane,Stirring under microwave reaction 10min,After completion of the reaction, the compound (1) (4.5 g, 99.2%, yield 75%) was isolated by silica gel column chromatography,
  • 33
  • [ 15905-16-5 ]
  • [ 90-45-9 ]
  • [ CAS Unavailable ]
  • [ CAS Unavailable ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
50% Stage #1: Pyridine-2,6-dicarboxylic acid N-oxide; aminacrine In methanol; water at 20℃; for 2h; Stage #2: nickel(II) nitrate hexahydrate; zinc(II) nitrate hexahydrate In methanol; water at 20℃; for 3h; Synthesis of {(H9a-acr)2[Ni0.51Zn0.49(pydco)2(H2O)2]·4H2O} (2) A methanolic solution of 9a-acr (0.2mmol, 40mg) was added dropwise to an aqueous solution of H2pydco (0.1mmol, 20mg) and the mixture was stirred at room temperature for 2h. Then Ni(NO3)2·6H2O (0.05mmol, 15mg) and Zn(NO3)2·6H2O (0.05mmol, 15mg) were added and the resulting reaction mixture was stirred for an additional 3h at the same temperature. Light yellow, plate-like crystals were obtained after 2weeks by slow evaporation of the reaction mixture at room temperature. (Yield: 50%; m.p. 200°C) Elemental analysis: Anal. Calcd. For: C40H40N6Ni0.51O16Zn0.49: C, 52.06; H, 4.38; N, 9.11%. Found: C, 52.11; H, 4.16; N, 9.44%. IR bands (KBr pellet, cm-1): 3404.5, 3053.3, 2968.8, 28 60.8, 1638.3, 1590.8, 1476.5, 1273.5, 1201.6, 770. Atomic absorption: Zn(49%) and Ni(51%).
  • 34
  • [ 90-45-9 ]
  • [ 57-10-3 ]
  • [ 2250294-11-0 ]
YieldReaction ConditionsOperation in experiment
55% Stage #1: 1-hexadecylcarboxylic acid With thionyl chloride In dichloromethane for 6h; Reflux; Inert atmosphere; Stage #2: aminacrine With triethylamine In dichloromethane at 20℃; for 12h; Synthesis of N-(acridine-9-yl)palmitamide(AC-PA). The synthesis ofthe AC-PA can be achieved by the modifiedprocedure [1-4]. To a solution of palmiticacid (3.9 mmol) in 20 ml of dry DCM, 0.4 ml of thionyl chloride (5.8mmol) was added. The mixture was refluxed for 6 h, and then the solvent wasremoved under reduced pressure, maintaining the inert atmosphere. Again, afteraddition of 10 ml of dry DCM, a solution of 9-aminoacridine (5.07 mmol) andtriethylamine (11.7 mmol) in 20 ml of DCM was added to the reaction mixture. The reaction mixture further stirred forovernight at room temperature. The solvent was removed under reduced pressureand the crude solid was extracted with ethyl acetate (3x100 ml). The combined organic phases were dried (MgSO4) and concentrated underreduced pressure. The resulted crude solid was purified by column chromatography (hexane/ ethyl acetate 50:50). Yellow solid. Yield = 55%.Rf: 0.4 (1:1, Ethyl acetate: Hexane). m.p. 310 C. IR (neat) (cm-1): 881, 1099, 1202, 1322, 1426, 1561, 1619, 1730, 2776, 2847, 2929, 3250. 1H NMR (500 MHz, DMSO (d6), δ (ppm): 0.76-0.85 (t, 3H); 1.23 (s, 24H); 1.47 (t, 2H); 2.16-2.18 (t, 2H);7.31-7.33 (t, 2H); 7.65 (s, 2H); 7.80-7.82 (d, 2H) and 8.38-8.40 (d, 2H).13C NMR (125 MHz, DMSO(d6), δ (ppm): 14.42, 22.56, 24.06, 25.01, 26.36, 27.82, 29.03, 29.21, 29.37, 29.50,31.76, 33.26, 34.24, 35.24, 35.98, 37.66, 113.40, 122.09, 123.79, 126.38, 130.52,142.70, 162.58, and 177.01.13C DEPT-135 (125 MHz, DMSO (d6), δ (ppm):14.60, 22.56, 23.24, 24.23, 25.01, 25.93, 27.21, 28.06, 29.04, 29.50,30.19, 31.89, 32.60, 34.24, 123.79, 128.70, and 130.53. HRMS (ESI, M+H+): m/z calcd. for C29H41N2Ois 433.3204, found 433.3219.
  • 35
  • [ 110166-26-2 ]
  • [ 61551-49-3 ]
  • N-(acridin-9-yl)-5,6,7,8-tetrahydronaphthalene-2-sulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
72% In ethanol at 20℃; 16 General procedure for the synthesis of N-(substituted)-5,6,7,8-tetrahydronaphthalene-2-sulfonamide 3-18 General procedure: A mixture of 5,6,7,8-tetrahydronaphthalene-2-sulfonyl chloride (1)(2.30 gm, 0.01 mol) and the appropriate primary amines namely; 2-methylaniline, 4-methylaniline, 4-acetylaniline, 3-fluoroaniline, 4-fluoroaniline, 3-chloroaniline, 4-chloroaniline, 2,4-dichloroaniline, 4-bromoaniline, 3-nitroaniline, 2-aminobenzoic acid, 4-aminobenzoicacid, 2-aminothiazole, 4-aminopyridine, 1-aminonaphthalene and/or 9-aminoacridine (0.01 mol) in absolute ethanol (10 mL) was continuouslystirred at room temperature overnight. The formed precipitate wasfiltered, washed several times with pet. ether, dried and crystallizedfrom ethanol to afford the title compounds 3-18 respectively.
  • 36
  • [ 90-45-9 ]
  • [ CAS Unavailable ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
72% With toluene-4-sulfonic acid at 150 - 180℃; Dean-Stark; 1.3 3,((3-((4,6-Difluorobenzo[d]thiazol-2-yl)methyl)thio)-1-(acridin-9-amino)-1-oxopropane-2-carboxylic acid (9H-fluoren-9-yl)yl carbamateSynthesis A suspension of compound 4 (11.51 g, 0.022 mol), acridin-9-amine (0.022 mol) and p-toluenesulfonic acid (~0.40 g) was placed in a mechanical stirrer.Add the reaction mixture to the oil bath and the round bottom flask of the Dean-Stark condenser.Thermal reflux (internal temperature 150-155 ° C,The oil bath temperature was 170-180 ° C) for 15-18 hours while monitoring the reaction by TLC.After completion of the reaction, the reaction was cooled to 80 ° C, and methanol (27 mL) was slowly added through a dropping funnel.After completion of the dropwise addition, the reaction mixture was slowly cooled to room temperature with stirring, and the obtained solid was filtered and washed with methanol (45 mL).And dried at 100-120 ° C for 2 hours.Get a white solid((3-((4,6-Difluorobenzo[d]thiazol-2-yl)methyl)thio))-1-(Acridine-9-ylamino)-1-oxopropane-2-carboxylic acid (9H-fluoren-9-yl)yl carbamate (Compound 5), 11.13 g, yield 72%.
72% With toluene-4-sulfonic acid at 150 - 180℃; Dean-Stark; 1.3 3,((3-((4,6-Difluorobenzo[d]thiazol-2-yl)methyl)thio)-1-(acridin-9-amino)-1-oxopropane-2- Formic acid (9H-fluoren-9-yl)yl)carbamateSynthesis Compound 4 (11.51 g, 0.022 mol),A suspension of acridine-9-ylamine (0.022 mol) and p-toluenesulfonic acid (~0.40 g) was placed in a mechanical stirrer.In a round bottom flask with an oil bath and a Dean-Stark condenser,The reaction mixture was heated to reflux (internal temperature 150-155 ° C,Oil bath temperature 170-180 ° C) 15-18 hours,The reaction was monitored by TLC at the same time.After the reaction is completed,The reaction was cooled to 80 ° C.Slowly added methanol (27 mL) through a dropping funnel.After the addition is completed,The reaction mixture was slowly cooled to room temperature with stirring.The resulting solid was filtered and washed with methanol (45 mL).And dried at 100-120 ° C for 2 hours.Obtained as a white solid ((3-((4,6-difluorobenzo[d]thiazol-2-yl)methyl)thio)-1-(acridin-9-ylamino)-1-oxo Propane-2-carboxylic acid (9H-fluoren-9-yl)yl carbamate (compound 5),11.13g,The yield was 72%.
  • 37
  • [ 90-45-9 ]
  • [ 86-81-7 ]
  • [ 2250213-36-4 ]
YieldReaction ConditionsOperation in experiment
73% In ethanol at 80℃; for 4h; 1.2 (2) Synthesis of fluorescent probe 0.26 mmol of 9-aminoacridine was dissolved in ethanol in a round bottom flask, and 0.312 mmol of 3,4,5-trimethoxybenzaldehyde was added thereto, and refluxed in ethanol at 80 °C for 4 h. Recrystallization gave the desired fluorescent probe 3 in 73% yield.
  • 38
  • [ 90-45-9 ]
  • [ 2248017-60-7 ]
  • [ 2248017-62-9 ]
YieldReaction ConditionsOperation in experiment
72% With toluene-4-sulfonic acid at 170 - 180℃; Dean-Stark; 1.3 3. Synthesis of ((3-((4,6-difluorobenzo[d]thiazol-2-yl)methyl)thio)-1-(acridin-9-amino))-1-oxopropane-2-carboxylic acid (9H-fluoren-9-yl)ylcarbamate Compound 4 (11.51 g, 0.022 mol), Acridine-9-ylamine (0.022 mol) and a suspension of p-toluenesulfonic acid (~0.40 g) was placed in a mechanical stirrer, In a round bottom flask with an oil bath and a Dean-Stark condenser, The reaction mixture was heated to reflux (internal temperature 150-155 ° C, Oil bath temperature 170-180 ° C) 15-18 hours, The reaction was monitored by TLC at the same time. After the reaction is completed, The reaction was cooled to 80 ° C. Slowly added methanol (27 mL) through a dropping funnel.After the addition is completed, The reaction mixture was slowly cooled to room temperature with stirring. The resulting solid was filtered and washed with methanol (45 mL).And dried at 100-120 ° C for 2 hours. Obtained as a white solid ((3-((4,6-difluorobenzo[d]thiazol-2-yl)methyl)thio)-1-(acridin-9-ylamino)-1-oxo Propane-2-carboxylic acid (9H-fluoren-9-yl)yl carbamate (Compound 5), 11.13 g, yield 72%.
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