* 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.
Reference:
[1] Journal of Medicinal Chemistry, 2007, vol. 50, # 15, p. 3515 - 3527
2
[ 53055-05-3 ]
[ 70127-96-7 ]
Yield
Reaction Conditions
Operation in experiment
64%
With hydrogenchloride; iron; acetic acid In ethanol at 0℃; for 0.333333 h; Heating / reflux
Example 2 Step 1. Preparation of 2-chloro-8-methoxyquinazolineStep 1. Preparation of 2-amino-3-methoxybenzaldehydeIron powder (40 g) was slowly added to a stirred solution of 3-methoxy-2-nitrobenzaldehyde (1) (70 g, 386 mmole) in AcOH gal. (100 mL) and EtOH abs. (400 mL). The reaction was cooled using an ice bath followed by addition of con. HCL (1 mL). The reaction became exothermic. After stabilization of the reaction temperature, the reaction was heated to reflux. The reaction reached completion after ca. 20 minutes according to LCMS. The reaction mixture was cooled to RT and filtered. The filtrate was evaporated to a thick brown syrup. The dark residue was dissolved in EtOAc (500 mL) and water (200 mL). The mixture was basified with NaOH 6M to ca. pH 10. The mixture was filtered over celite and the layers separated. The organic layer was washed with NaHCO3 (2 x 100 mL), water (2 x 100 mL), brine (100 mL), dried (Na2SO4), filtered and evaporated to a dark amber oil. The oil was dried in vacuo to give 95percent pure product 2-amino-3-methoxybenzaldehyde in 64percent yield (37.2 g, 246 mmole).
24%
With ammonium chloride; zinc In ethanol at 70℃; for 3 h;
To a solution of 3-methoxy-2-nitrobenzaldehyde (15.0 g, 83 mmol) in ethanol (450 mL) was added ammonium chloride (31.0 g, 580 mmol) and zinc powder (43.3 g, 662 mmol). The reaction mixture was heated at 70 °C for 3 h. The reaction mixture was cooled to room temperature and was filtered through a pad of Celite. The filtratewas concentrated and the residue was purified by column chromatography on silica gel (20percent —* 30percent ethyl acetate in hexanes) to afford 2-amino-3- methoxybenzaldehyde (2.94 g, 24percent yield) as a yellow oil: ‘H NMR (400 MHz, CDC13) ö 9.91 (s, 1H), 7.15 (dd, J 8.0, 1.2 Hz, 1H), 6.90 (dd, J 7.7, 0.9 Hz, 1H), 6.71 (t, J 7.9 Hz, 2H), 6.42 (br s, 2H), 3.91 (s, 3H); MS (ESI) m/e 152.1 [(M+H),calcd for C8H10NO2 152.1].
Reference:
[1] Inorganic Chemistry, 2011, vol. 50, # 21, p. 10966 - 10973
[2] Patent: WO2007/117607, 2007, A2, . Location in patent: Page/Page column 306
[3] Journal of Medicinal Chemistry, 2007, vol. 50, # 15, p. 3515 - 3527
[4] Patent: WO2016/53794, 2016, A1, . Location in patent: Page/Page column 63; 64
[5] Journal of the Chemical Society, 1925, vol. 127, p. 876,877[6] Journal of the Chemical Society, 1926, p. 150
[7] Journal fuer Praktische Chemie (Leipzig), 1925, vol. <2> 111, p. 211
[8] Journal fuer Praktische Chemie (Leipzig), 1926, vol. <2> 114, p. 231,235
[9] Chemical and Pharmaceutical Bulletin, 1962, vol. 10, p. 856 - 865
[10] Patent: US2003/97000, 2003, A1,
[11] Patent: US6617336, 2003, B1,
[12] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 7, p. 2664 - 2671
3
[ 205877-13-0 ]
[ 70127-96-7 ]
Yield
Reaction Conditions
Operation in experiment
74%
With manganese(IV) oxide In dichloromethane at 20℃; for 23 h; Inert atmosphere
General procedure: To a solution of 1a (1.2 g, 7.61 mmol) in CH2Cl2 (20 mL) was added MnO2 (2.6 g, 30.1 mmol) and stirred at rt under an Ar atmosphere. After 23 h with stirring, the reaction mixture was filtrated and evaporated. The residue was crystallized from AcOEt to give 7a (1.0 g, 85percent) as a yellow needle crystal.
Reference:
[1] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 19, p. 5810 - 5831
[2] Organic and Biomolecular Chemistry, 2017, vol. 15, # 31, p. 6474 - 6477
4
[ 53055-05-3 ]
[ 70127-96-7 ]
[ 122528-40-9 ]
Yield
Reaction Conditions
Operation in experiment
53%
With vasicine In ethylene glycol at 80℃; for 48 h;
General procedure: The mixture of nitrocompound (0.5 mmol) and vasicine (0.5 mmol) in ethylene glycol (2 mL) was stirred at 80°C for 24-48 h. Time was not optimized separately for all substrates. After completion of reaction as monitored by TLC, the reaction mixture was cooled to ambient temperature and extracted with ethyl acetate. The ethyl acetate layer was dried under reduced pressure using rotatory evaporator. The crude was chromatographed over silica gel to afford the desired product.
With manganese(IV) oxide; In dichloromethane; at 20℃; for 23h;Inert atmosphere;
General procedure: To a solution of 1a (1.2 g, 7.61 mmol) in CH2Cl2 (20 mL) was added MnO2 (2.6 g, 30.1 mmol) and stirred at rt under an Ar atmosphere. After 23 h with stirring, the reaction mixture was filtrated and evaporated. The residue was crystallized from AcOEt to give 7a (1.0 g, 85%) as a yellow needle crystal.
With triethylammonium acetate In neat (no solvent) at 60℃; for 0.5h;
General procedure for the addition of 3,5-dimethyl-4-nitroisoxazole-C(sp3)-H bond to substituted o-amino benzaldehydes (6a-k)
General procedure: A mixture of 3,5-dimethyl-4-nitroisoxazole 4 (1 mmol) and substituted o-amino benzaldehyde 5 (1 mmol) were taken in triethyl amino acetic acid (TEAA) ionic liquid (5 mL) and the reaction mixture was stirred at 60 °C. After the completion of the reaction (monitored by TLC), the reaction mixture was extracted with diethyl ether. The combined layers were separated and dried over anhyd. Na2SO4, and evaporated under reduced pressure to afford the crude products (6a-k). The ionic liquid left over in the reaction was washed with ethyl acetate and dried over 80 °C under vacuum and was reused for 5 consecutive runs. The procedure was followed for all the reactions, as listed in Table 2.
5-methoxy-3-phenyl-3,4-dihydroacridin-1(2H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
80%
With hydrogenchloride In water at 75 - 80℃;
General procedure for the synthesis of acridone derivatives
General procedure: To a mixture of substituted 2-aminebenzaldehyde (1.0 mmol) and 5-substituted-1,3-cyclohexanedione (1.2 mmol), 1 ml of 1 N HCl aqueous solution was added. The resulting mixture was stirred at 75-80 0C. After completion of the reaction (monitored by TLC), the resulting suspension was neutralized with 1 mL of 1 N NaOH. The solid was filtered, washed with water (3× 6 mL), and air-dried to give the product as white or slightly yellow powder. The solid product was further purified by recrystallization with ethanol when necessary.
With [RuCl2pentamethylcyclopentadiene]n; silver trifluoroacetate; trifluoroacetic acid In 2,2,2-trifluoroethanol at 80℃; for 8h;
37 Example 37
The preparation method of compound I-13,Including the following process: 0.2mmol of 2-amino-3-methoxybenzaldehyde,Isoxazole 0.3mmol,Dichloro (pentamethylcyclopentadienyl) ruthenium () 0.005mmol,Silver trifluoroacetate 0.02mmol,Add 0.2mmol trifluoroacetic acid to the reaction tube,Dissolved in an appropriate amount of trifluoroethanol solvent,React at 80 for 8 hours,The reaction solution was filtered through diatomaceous earth, and the filtrate was concentrated,Purification by column chromatography gave 32.0 mg of the target product with a yield of 86%.
86%
With bis[dichloro(pentamethylcyclopentadienyl)ruthenium(III)]; silver trifluoroacetate; trifluoroacetic acid In 2,2,2-trifluoroethanol at 80℃; for 10h;
2. Typical Catalytic Procedure
General procedure: A reaction tube (15 mL) equipped with a magnetic stirrer bar was charged with 2-aminobenzaldehyde 1a (0.1 mmol), isoxazole 2a (0.12 mmol), [Cp*RuCl2]2 (2.5 mol %), CF3COOAg (10 mol %), CF3COOH (1 equiv.) in anhydrous CF3CH2OH (1.5 mL). The reaction mixture was stirred at 80 for 10 h under air atmosphere. When the reaction was completed, the mixture was cooled to room temperature and then purified by column chromatography on silica gel with ethyl acetate/petroleum ether (1:5) to give the desired product 3a.