There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.
Type
HazMat fee for 500 gram (Estimated)
Excepted Quantity
USD 0.00
Limited Quantity
USD 15-60
Inaccessible (Haz class 6.1), Domestic
USD 80+
Inaccessible (Haz class 6.1), International
USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic
USD 100+
Accessible (Haz class 3, 4, 5 or 8), International
USD 200+
Structure of 102-51-2 * Storage: {[proInfo.prStorage]}
* 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] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 7, p. 2620 - 2623
2
[ 68-12-2 ]
[ 102-51-2 ]
[ 4887-80-3 ]
Yield
Reaction Conditions
Operation in experiment
93%
at 120℃; for 6 h;
General procedure: To a 10mL three-necked round bottle was charged with 1a (0.54 g, 5 mmol), imidazolium chloride (0.09 g, 0.5 mmol) and N,N-dimethylformamide 2 mL. The resulting solution was warmed to120 °C and stirred at this temperature for 6 h. When the reaction was completed, 25 mL water was added and the resulting mixture was extracted with 25 mL ethyl acetate twice. The combined organic layer was successively washed with H2O (50 mL) and then brine (50 mL), then dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel with petroleum ether and ethyl acetate or recrystallized from petroleum ether/EA to give the title products.
Reference：
[1] Green Chemistry, 2015, vol. 17, # 12, p. 5172 - 5181
8
[ 57-55-6 ]
[ 102-51-2 ]
[ 4887-80-3 ]
[ 4887-81-4 ]
Reference：
[1] Bulletin of the Chemical Society of Japan, 2010, vol. 83, # 7, p. 831 - 837
9
[ 107-21-1 ]
[ 102-51-2 ]
[ 6639-82-3 ]
[ 4887-80-3 ]
[ 92050-12-9 ]
Reference：
[1] Bulletin of the Chemical Society of Japan, 2010, vol. 83, # 7, p. 831 - 837
10
[ 55305-43-6 ]
[ 102-51-2 ]
[ 6232-91-3 ]
Yield
Reaction Conditions
Operation in experiment
66%
With lithium hexamethyldisilazane In tetrahydrofuran; hexane at 5 - 20℃; for 1 h; Green chemistry
General procedure: To a solution of o-aminophenol (400 mg, 3.67 mmol) and NCTS (998 mg, 3.67 mmol) in THF (6 mL), 1 M LiHMDS in hexane (3.67 mL, 3.67 mmol) was added and stirred at 5 °C to r.t. for 1h. Then the reaction mixture was poured in ice water and stirred for 15 min. Then extracted with EtOAc, the organic layer was separated. The organic layer was washed with brine solution.Then organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to obtained pure 2-aminobenzaxozole in 90percent yield (471 mg).
Reference：
[1] Angewandte Chemie - International Edition, 2012, vol. 51, # 21, p. 5226 - 5229
[2] European Journal of Medicinal Chemistry, 1991, vol. 26, # 6, p. 633 - 642
[3] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 23, p. 270
[4] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 11, p. 2842 - 2845
[5] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 23, p. 270
12
[ 103-82-2 ]
[ 102-51-2 ]
[ 40608-76-2 ]
Yield
Reaction Conditions
Operation in experiment
67%
With boric acid In 5,5-dimethyl-1,3-cyclohexadiene for 16 h; Reflux
General procedure: To a stirred solution of benzene-1,2-diamine 1 (1.85 mmol)in xylenes (10 mL) were added carboxylic acid 2 (2.77 mmol)and boric acid (0.185 mmol). The resulting solution wasrefluxed for 16 h. After cooling to room temperature, the reactionwas concentrated under reduced pressure and diluted withEtOAc (50 mL). The organic phase was washed with saturatedNaHCO3 solution (2 50 mL), dried over anhydrous Na2SO4and then concentrated under reduced pressure. The residuewas purified by silica gel flash column chromatography (elutingwith 10–15percent Ethyl acetate in hexanes) to afford the title compounds3a–y and 5.6.2.21 2-Benzyl-5-methoxy-1H-benzo[d]imidazole (3u) Yield 67percent; Off white solid; mp 109-111 °C; IR (KBr) 3009, 2847, 1510, 1466, 1410, 1248, 1175, 1029, 775 cm-1; 1H NMR (400 MHz, DMSO-d6) δ 12.04-12.14 (m, 1H), 7.18-7.44 (m, 6H), 6.91 - 7.07 (m, 1H), 6.70-6.79 (m, 1H), 4.12 (s, 2H), 3.75 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ 155.5, 137.9, 128.8, 128.5, 126.6, 118.7, 110.1, 101.3, 94.5, 55.4, 34.9; HRMS calcd for C15H14N2O m/z 238.1182, found 238.1180.
Reference：
[1] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 8, p. 1872 - 1878
[2] Zhurnal Obshchei Khimii, 1949, vol. 19, p. 1545,1550[3] J. Gen. Chem. USSR (Engl. Transl.), 1949, vol. 19, p. 1555
13
[ 122-78-1 ]
[ 102-51-2 ]
[ 40608-76-2 ]
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 7, p. 2620 - 2623
14
[ 102-51-2 ]
[ 27799-91-3 ]
Reference：
[1] European Journal of Medicinal Chemistry, 2010, vol. 45, # 6, p. 2214 - 2222
[2] Journal of the American Chemical Society, 1953, vol. 75, p. 715,717
15
[ 102-51-2 ]
[ 27799-91-3 ]
Reference：
[1] Organic and Biomolecular Chemistry, 2014, vol. 12, # 2, p. 251 - 254
16
[ 67-56-1 ]
[ 102-51-2 ]
[ 10394-42-0 ]
[ 10394-39-5 ]
[ 4887-80-3 ]
Reference：
[1] Green Chemistry, 2015, vol. 17, # 12, p. 5172 - 5181
17
[ 924-44-7 ]
[ 102-51-2 ]
[ 55687-11-1 ]
Yield
Reaction Conditions
Operation in experiment
35%
Stage #2: for 1 h; Reflux
Step A: 7-Methoxyqu lin-2(lH)-oneA 50percent solution of ethyl 2-oxoacetate (18.47 mL, 93 mmol) in toluene was added to a solution of 4-methoxybenzene-l,2-diamine (10.73 g, 78 mmol) in ethanol (100 mL) at ambient temperature and the reaction was refluxed for 2 h. The reaction was concentrated in vacuo and crystallized from ethanol to afford a mixture of 6- methoxyquinoxalin-2(lH)-one and 7-methoxyquinoxalin-2(lH)-one (5.73 g, 32.50 mmol, 42 percent yield). MS (LC/MS) R.T. = 0.68; [M+H]+ = 177.10.
35%
Stage #1: at 20℃; for 2 h; Reflux Stage #2: for 1 h; Reflux
50percent solution of ethyl2-oxoacetate (18.47 ml., 93mmol) in toluene was added to a solution of 4-methoxybenzene-I,2-diamine (10.73 g, 78 mmol) in ethanol (100 mL) at ambient temperature and the reaction was ref/uxed for 2 h.The reaction was concentrated in vacuo and crystallized fromethanol to afford a mixture of 6-methoxyquinoxalin-2(1H)oneand 7-methoxyquinoxalin-2(1H)-one (5.73 g, 32.50mmol, 42percent yield). A mixture of 6-methoxyquinoxalin-2(1H)-one and7-methoxyquinoxalin-2(1H)-one (5.67 g, 32.20 mmol) wasrefluxed in phosphorus oxychloride (120 mL) for I h. Thereaction was concentrated and quenched by addition of ice,then basified with sodium carbonate, and extracted with ethylacetate (3x200 mL). The organic layers were combined andconcentrated in vacuo. The crude product was absorbed ontosodium sulfate and purified by column chromatography (0 to5percent ethyl acetatelhexanes) to afford 2-chloro-6-methoxyquinoxaline(2.21 g, 11.36 mmol, 35percent yield).
To a solution of 4-methoxybenzene-1,2-diamine (5 g, 36.2 mmol) in ethanol (50 ml) was added ethyl 2-oxoacetate (4.06 g, 39.8 mmol)). The reaction mass was heated at reflux for overnight. The solvent was evaporated under reduced pressure and the residue was diluted with ethyl acetate and then evaporated to dryness to get the crude compound. The crude compound was washed with pet ether to get crude compound (5.1 g, 80percent yield) as a mixture of regioisomers (black solid). This crude compound was taken to the next step without separation of isomers.1H NMR (400 MHz, DMSO-d6): δ ppm 8.17 (s, 1H), 7.98 (s, 1H), 7.70-7.68 (d, J=8 Hz, 1H), 7.31-7.30 (d, J=4 Hz, 1H), 7.27-7.20 (m, 2H), 6.93-6.90 (m, 1H), 6.77-6.76 (d, J=4 Hz, 1H), 3.84 (s, 3H), 3.83 (s, 3H); MS: MS m/z 177.0 (M++1). A solution of 6-methoxyquinoxalin-2(1H)-one & 7-methoxyquinoxalin-2(1H)-one (3 g, 18.28 mmol) in POCl3(20 ml) was refluxed for 3 h. The solvent was evaporated under reduced pressure and the residue was diluted with cold water. The aqueous solution was basified by solid sodium carbonate and extracted with ethyl acetate. The combine organic layer was dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure to get crude compound. The crude compound was purified by silica gel chromatography (20percent ethyl acetate in pet ether) to afford mixture of regioisomers (3.7 g). 2 g of the above mixture was separated by SFC purification to afford 2-chloro-7-methoxyquinoxaline (0.7 g, 34.7percent) and 2-chloro-7-methoxyquinoxaline (0.9 g, 44.6percent) as off white solid.2-chloro-6-methoxyquinoxaline:1H NMR (400 MHz, DMSO-d6): δ ppm1H NMR (400 MHz, CDCl3): δ ppm 8.71 (s, 1H), 7.91-7.89 (d, J=8 Hz, 1H), 7.46-7.38 (m, 2H), 3.97 (s, 3H); MS: MS m/z 194.9 (M++1).2-chloro-7-methoxyquinoxaline:1H NMR (400 MHz, CDCl3): δ ppm 8.63 (s, 1H), 7.99-7.96 (d, J=12 Hz, 1H), 7.43-7.40 (d, J=12 Hz, 1H), 7.30 (s, 1H), 3.96 (s, 3H); MS: MS m/z 194.9 (M++1).
150 mg
Stage #1: for 2 h; Reflux Stage #2: for 1 h; Reflux
To a solution of 4-methoxybenzene-1,2-diamine (3.58 g, 25.9 mmol) in dry EtOH (30 mL) was added 50percent ethyl 2-oxoacetate in toluene (6.2 mL) and the mixture was heated under reflux for 2 h. After cooling to rt, the mixture was concentrated under reduced pressure. The residue was washed with EtOH to give a mixture of 6-methoxyquinoxalin-2-ol and 7-methoxyquinoxalin-2-ol as a brown solid (2.6 g, 57percent). 1H NMR (300 MHz, DMSO-d612.30 (s, 1H), 8.13 (s, 1H), 7.23-7.25 (m, 1H), 7.15-7.20 (m, 2H), 3.78 (s, 3H). LC-MS (ESI) mlz 177 (M+H)+. [000179] Step 2: The mixture of 6-methoxyquinoxalin-2-ol and 7-methoxyquinoxalin-2-ol (1.6 g, 9.1 mmol) in POC13 (30 mL) was heated under reflux for 1 h. After cooling to rt, the reaction mixture was concentrated under reduced pressure. The residue was quenched with ice, basified with saturated aq Na2CO3, and extracted with EtOAc. The organic layer was dried over Na2504, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 3percent EtOAc in petroleum ether to give the following products:[000180] Pure 2-chloro-6-methoxyquinoxaline as a white solid (150 mg), 1H NMR (300 MHz, CDC13 8.71 (s, 1H), 7.90 (d, J = 9.3 Hz, 1H), 7.44 (dd, J = 9.3, 2.7 Hz, 1H), 7.37 (d, J = 2.7 Hz, 1H), 3.95 (s, 3H). LC-MS (ESI) mlz 195 (M+H)+.[000181] Pure 2-chloro-7-methoxyquinoxaline as a white solid (100 mg). 1H NMR (300 MHz, CDC13 8.62 (s, 1H), 7.97 (d, J = 9.3 Hz, 1H), 7.41 (dd, J = 9.3, 2.7 Hz, 1H), 7.29 (d, J = 2.7 Hz, 1H), 3.96 (s, 3H). LC-MS (ESI) mlz 195 (M+H)+.[000182] A mixture of 2-chloro-6-methoxy quinoxaline and 2-chloro-7- methoxyquinoxaline as a white solid (1.27 g, 85percent).
Reference：
[1] Journal of the Chemical Society. Perkin Transactions 1, 2001, # 9, p. 978 - 984
31
[ 3395-03-7 ]
[ 102-51-2 ]
[ 27841-33-4 ]
Reference：
[1] Patent: US6218415, 2001, B1,
32
[ 96-96-8 ]
[ 102-51-2 ]
Yield
Reaction Conditions
Operation in experiment
99%
With palladium 10% on activated carbon; hydrogen In ethanol at 20℃; for 24 h;
Approximately 360 mg (2.14 mmol) of 4-methoxy-2-nitroanniline was placed in a hydrogenator and 65 mL ethanol was added. A pinch of 10percent palladium on activated carbon was added and the reaction mixture hydrogenated at room temperature under 50 Psi pressure for 24 hrs. The reaction mixture was filtered and concentrated on rotovap to give TZ10-55 as dark purple oil (294 mg, 2.12 mmol, 99percent). 1HNMR (CDCl3): δ 6.64 (d, J=8.7 Hz, 1H), 6.35-6.30 (m, 1H), 6.26 (d, J=8.7 Hz, 1H), 3.52 (s br, 2H), 3.07 (s br, 2H).
97%
With hydrogen In methanol at 20℃;
Example 68: T-chloro-B-oxo-B^-dihydro^H-benzon^lthiazine--carboxylic acid {1- [2-f7-methoxy-3-methyl-quinoxalin-2-yloxy)-ethyll-piperidin-4-yl}-amide: Preparation of 4-methoxy-benzene-l ,2-diamine: 10percent Palladium on activated carbon (1.0 g, 9.4 mmol, 0.15 eq) is added at room temperature to a stirred solution of 4-methoxy-2-nitro-phenylamine (10.0 g, 59.5 mmol, 1.0 eq) in methanol (70 mL). The mixture is hydrogenated for 72 hours, then filtered through decalite. Solvent is removed to afford 4-methoxy-benzene-l,2-diamine as a dark brown oil (8.0 g, 97percent yield).1H-NMR (400 MHz, MeOH-t/4) δ ppm: 6.62 (d, J = 8.4 Hz, IH), 6.34 (d, J = 2.8 Hz, IH), 6.18 (dd, J = 2.8, 8.4 Hz, IH), 3.82 (s, 3H).
84.5%
With iron; ammonium chloride In ethanol; water for 24 h; Reflux
To a stirred solution of 4-methoxy-2-nitroaniline (8.7 g, 51.73 mmol) in EtOHJH2O(3:1, 105 mL) was added portion wise Fe powder (20.5 g, 36.73 mmol) followed byNH4C1 at room temperature. The reaction mixture was heated at reflex for 24h. Aftercompletion of the reaction, filtered through a small pad of Celite and washed withEtOH (3 X 30 mL), solvent was evaporated under reduced pressure. The obtainedcrude was dissolved in H20 (50 mL) and extracted with EtoAc (3 X 60 mL). Thecombined organic layers were dried over anhydrous Na2504, filtered and concentrated under reduced pressure to get a 84.5 percent yield of dark brown colour solid, which was used in the next step without any further purification. ‘H NMR (500 MHz, DMSO-d6):5 6.50 (d, 1H), 6.20 (d, 1H), 6.00 (dd, 1H), 3.50 (s, 3H). LC-MS [mlz]: 139.2 [M+H],91.670percent purity.
72.5%
With palladium on activated charcoal; hydrogen In methanol at 50℃;
To a mixture of compound 1 (33.6 g, 0.020 mol) and Pd/C (6.72 g) in MeOH (400 mL) was hydrogenated under 50 psi of H2 at 50° C. for 3 h. The catalyst was filtered off and the filtrate was concentrated to give the residue then purified by column chromatography on silica gel to give compound 2 (20 g, 72.5percent) as reddish solid.
69%
With iron; ammonium chloride In ethanol; waterReflux
Intermediate 35:[0166] To a solution of 4-methoxy-2-nitroaniline (10 g, 59.4 mmol) in EtOH (200 mL) and water (80 mL) was added iron (12 g, 210 mmol) and ammonium chloride (9.63 g, 180 mmol). The mixture was then heated to reflux and stirred overnight. The mixture was filtered and the filtrate was evaporated to remove the EtOH and the residue was purified by flash chromatography on silica gel column (elution with DCM/MeOH = 80:1) to give 4- methoxybenzene-l,2-diamine (intermediate 35) (5.65 g, 69percent) as a yellow solid.
95 %Chromat.
With hydrazine hydrate In ethanol at 80℃; for 1 h; Inert atmosphere
General procedure: Hydrazine hydrate was chosen as the hydrogen donor for the low emission of pollutants. In a typical procedure, hydrazine hydrate (4 equiv) was added into the reactor which containing fresh prepared catalyst as described above. Then the reactor was put into a preheated oil bath with a stirring speed of 500 rpm, and the substrate (1 mmol)dissolved in 1 mL ethanol was added drop-wisely under argon. The reactions were monitored by TLC. After the reaction, the reaction mixture was vacuum filtered through a pad of silica on a glass-fritted funnel and an additional 15 mL of ethyl acetate (5 mL portions) was used to rinse the product from the silica, the filtrate was concentrated in vacuum and analyzed by GC. Products were purified by column chromatography and identified by 1H NMR and 13C NMR.
Reference：
[1] Patent: US2013/315825, 2013, A1, . Location in patent: Paragraph 0220
[2] Patent: WO2010/84152, 2010, A1, . Location in patent: Page/Page column 109-110
[3] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2006, vol. 45, # 7, p. 1756 - 1758
[4] RSC Advances, 2015, vol. 5, # 78, p. 63421 - 63428
[5] Patent: WO2017/37604, 2017, A1, . Location in patent: Page/Page column 25
[6] Patent: JP2015/214548, 2015, A, . Location in patent: Paragraph 1288; 1289
[7] RSC Advances, 2018, vol. 8, # 12, p. 6288 - 6292
[8] Patent: WO2012/3418, 2012, A2, . Location in patent: Page/Page column 70
[9] European Journal of Medicinal Chemistry, 1991, vol. 26, # 6, p. 633 - 642
[10] Chemical Communications, 2014, vol. 50, # 56, p. 7469 - 7472
[11] Journal of the American Chemical Society, 1947, vol. 69, p. 795,796
[12] Zhurnal Obshchei Khimii, 1949, vol. 19, p. 1545,1550[13] J. Gen. Chem. USSR (Engl. Transl.), 1949, vol. 19, p. 1555
[14] Journal of the American Chemical Society, 1947, vol. 69, p. 795,796
[15] Zhurnal Obshchei Khimii, 1949, vol. 19, p. 1545,1550[16] J. Gen. Chem. USSR (Engl. Transl.), 1949, vol. 19, p. 1555
[17] Journal of the Chemical Society, 1948, p. 1719
[18] Journal of the American Chemical Society, 1947, vol. 69, p. 583,58
[19] Acta Chemica Scandinavica, 1992, vol. 46, # 11, p. 1109 - 1113
[20] Farmaco, 1994, vol. 49, # 10, p. 671 - 674
[21] Bioorganic and Medicinal Chemistry, 1998, vol. 6, # 2, p. 163 - 172
[22] Journal of the American Chemical Society, 2006, vol. 128, # 26, p. 8569 - 8574
[23] Tetrahedron Letters, 2006, vol. 47, # 30, p. 5359 - 5361
[24] Journal of Heterocyclic Chemistry, 2009, vol. 46, # 2, p. 221 - 225
[25] Journal of Medicinal Chemistry, 2010, vol. 53, # 21, p. 7664 - 7674
[26] Journal of the American Chemical Society, 2012, vol. 134, # 18, p. 7604 - 7607
[27] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 17, p. 4790 - 4793
[28] Asian Journal of Chemistry, 2013, vol. 25, # 14, p. 7959 - 7966
[29] Dyes and Pigments, 2013, vol. 99, # 3, p. 1132 - 1136
[30] Journal of the Serbian Chemical Society, 2014, vol. 79, # 3, p. 277 - 282
[31] Molecules, 2014, vol. 19, # 7, p. 9736 - 9759
[32] Patent: WO2014/145095, 2014, A1, . Location in patent: Page/Page column 106
[33] ChemMedChem, 2015, vol. 10, # 3, p. 511 - 522
[34] Patent: WO2015/95430, 2015, A1, . Location in patent: Page/Page column 52
[35] Tetrahedron Letters, 2015, vol. 56, # 48, p. 6762 - 6767
[36] Organic Letters, 2016, vol. 18, # 9, p. 1952 - 1955
[37] Catalysis Communications, 2016, vol. 84, p. 25 - 29
[38] Patent: CN106212487, 2016, A, . Location in patent: Paragraph 0032
[39] Patent: CN106243110, 2016, A, . Location in patent: Paragraph 0027; 0028
[40] Patent: CN104710815, 2017, B, . Location in patent: Paragraph 0059; 0060; 0061
[41] Patent: CN104710817, 2017, B, . Location in patent: Paragraph 0052-0055
[42] Patent: CN104710816, 2017, B, . Location in patent: Paragraph 0054; 0055; 0056; 0057
33
[ 16133-49-6 ]
[ 102-51-2 ]
Yield
Reaction Conditions
Operation in experiment
24 g
With palladium 10% on activated carbon; hydrogen In methanol
32 g of 5-methoxy-2-nitroaniline was added to 350 ml of methanol, 3.2 g of 10percent palladium carbon was added, hydrogen was bubbled in, stirred overnight, filtered, the filtrate was collected, and concentrated to give 24 g of 4-methoxy-1 2-diphenylamine.
Reference：
[1] Journal of Heterocyclic Chemistry, 1987, vol. 24, # 6, p. 1771 - 1775
[2] Synthetic Communications, 2007, vol. 37, # 19, p. 3455 - 3470
[3] Journal of Heterocyclic Chemistry, 2012, vol. 49, # 5, p. 1196 - 1201
[4] Patent: JP2016/175996, 2016, A, . Location in patent: Paragraph 0147-0148
[5] Patent: CN106234372, 2016, A, . Location in patent: Paragraph 0027
[6] Patent: JP2016/172816, 2016, A, . Location in patent: Paragraph 0112-0113
[7] Patent: CN106220575, 2016, A, . Location in patent: Paragraph 0025; 0026
[8] Journal of Medicinal Chemistry, 2017, vol. 60, # 14, p. 6289 - 6304
[9] Patent: CN107778252, 2018, A, . Location in patent: Paragraph 0020-0022
Reference：
[1] Journal of Organic Chemistry, 2012, vol. 77, # 15, p. 6653 - 6656
37
[ 4280-28-8 ]
[ 102-51-2 ]
Reference：
[1] Journal of the American Chemical Society, 1958, vol. 80, p. 1662
38
[ 119-81-3 ]
[ 102-51-2 ]
Reference：
[1] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2006, vol. 45, # 7, p. 1756 - 1758
[2] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2006, vol. 45, # 7, p. 1756 - 1758
[3] Asian Journal of Chemistry, 2013, vol. 25, # 14, p. 7959 - 7966
[4] Patent: WO2017/37604, 2017, A1,
39
[ 51-66-1 ]
[ 102-51-2 ]
Reference：
[1] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2006, vol. 45, # 7, p. 1756 - 1758
[2] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2006, vol. 45, # 7, p. 1756 - 1758
[3] Asian Journal of Chemistry, 2013, vol. 25, # 14, p. 7959 - 7966
[4] Patent: WO2017/37604, 2017, A1,
40
[ 104-94-9 ]
[ 102-51-2 ]
Reference：
[1] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2006, vol. 45, # 7, p. 1756 - 1758
[2] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2006, vol. 45, # 7, p. 1756 - 1758
[3] Asian Journal of Chemistry, 2013, vol. 25, # 14, p. 7959 - 7966
[4] Patent: WO2017/37604, 2017, A1,
41
[ 5228-61-5 ]
[ 102-51-2 ]
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 17, p. 4790 - 4793
EXAMPLE 4 2-[(3,7-Dimethyl-2,6(E)-octadienyl)thio]-5-methoxy-1H-1,3-benzimidazole Monooxalate To potassium hydroxide (3.8 g, 0.067M) in ethanol (20 mL) and water (7 mL) was added 2.5 mL CS2 (3.09 g, 0.04M) (H2 S trapped over clorox). The reaction mixture was stirred for 30 minutes at ambient temperature, cooled to 0° C., and 4-methoxy-o-phenylene diamine (5.23 g, 0.03M) was slowly added. This reaction mixture was then stirred at reflux for 4 hours, stirred at ambient temperature overnight (basic soln. with pH paper), evaporated in vacuo and diluted with CH2 Cl2. Addition of water gave a precipitate which was suspended in CH2 Cl2 and acidified to pH 4. Filtration of the suspension gave purple crystalline 5-methoxy-2-mercaptobenzimidazole (3.4 g, 63percent).
Reference：
[1] Patent: US5106863, 1992, A,
44
[ 75-15-0 ]
[ 102-51-2 ]
[ 37052-78-1 ]
Reference：
[1] Medicinal Chemistry Research, 2014, vol. 23, # 3, p. 1290 - 1299
[2] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2006, vol. 45, # 7, p. 1756 - 1758
[3] European Journal of Medicinal Chemistry, 2003, vol. 38, # 9, p. 811 - 824
45
[ 140-89-6 ]
[ 102-51-2 ]
[ 37052-78-1 ]
Reference：
[1] Chemical and Pharmaceutical Bulletin, 1989, vol. 37, # 6, p. 1517 - 1523
46
[ 140-92-1 ]
[ 102-51-2 ]
[ 37052-78-1 ]
Reference：
[1] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2012, vol. 51, # 11, p. 1619 - 1622
47
[ 63467-57-2 ]
[ 102-51-2 ]
[ 37052-78-1 ]
Reference：
[1] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2012, vol. 51, # 11, p. 1619 - 1622
With palladium on activated charcoal; hydrogen In methanol
With 5%-palladium/activated carbon; hydrogen In methanol at 20 - 30℃; for 0.5h; Autoclave;
1.8 [Synthesis of (A) Dye] [Example 1]
15.2 parts of 2-methyl-6-nitroaniline was dissolved in 300 parts of methanol. The obtained solution was transferred into an autoclave, 2.0 parts of 5% Pd / carbon was added, reacted at 20 ° C. to 30 ° C. under a hydrogen pressure of 0.2 MPa-0.5 MPa until absorption of hydrogen ceased, The reaction was further continued at the same temperature for 30 minutes. The catalyst (5% Pd / carbon) was separated by filtration to obtain a solution (filtrate) containing the compound represented by the following formula (24).
With hydrazine hydrate In methanol Reflux;
In a 250 ml single-mouth flask, add 0.1 mol 5-methoxy-o-nitroaniline, 40 ml methanol, 75 ml hydrazine hydrate (85%), 0.25-0.45 Raney Ni (wet weight). Heat to reflux. for the disappearance of the TCL tracking to the raw materials, the reaction after cooling to room temperature, filtering to remove the Raney Ni, reduced pressure distillation to remove the solvent to obtain the light brown crystal, to get the formula 1 compound of formula 1 o-phenylenediamine. In a 250 ml single-mouth flask, add the 0.1 mol o-phenylenediamine. Use 100 ml ethanol to dissolve. Then slowly add dropwise MBF. During the add dropwise process, yellow solid appears. According to the substituent R1 changes, different reaction time, the reaction time at room temperature for 30-120 min, after the reaction is complete, filtering to remove the solvent, washing three times with ethanol, to obtain the formula 2 compound 7-methoxy-2-hydroxy-3-phenylquinoxaline. The compound 2 was added in 40 mL POCl3 as the solvent. Under the condition of heating and refluxing, chlorinated. for the disappearance of the TLC tracking to the raw materials, after the reaction cooled to the room temperature, slowly poured into the 500g ice water, immediately separate out a large amount of yellow solid, filtering, washing and drying, to obtain the compound of formula 3. In 250 ml three-mouthed flasks, add compound 3 and use 60 ml ethanol as solvent. Slowly add dropwise 18g (0.3 mol) 85% hydrazine hydrate. After adding dropwise, heat to reflux. React for 4-5h. After the reaction cooled to room temperature, poured into the 300g the ice water, immediately separate out a large amount of white solid, after filtering, washing and drying, the obtained crude product, through re-crystallization is shown as formula 4 represented compound 4. In a 50 ml round bottom flask was added 0.377g (0.002 mol) of the hydrazine, add 15 ml ethanol as solvent. Under stirring conditions, slowly add dropwise 0.002 mol substituted aldehyde compound, the raw material is quickly dissolved, then solid is precipitated out. Stir at room temperature overnight. board monitoring, the raw material after the reaction is complete, filtering, petroleum ether and ethanol mixed solution for washing three times, be red yellow solid powder, that formula (I) shown in benzene and pyrazine structure of the hydrazone compound.
With 5%-palladium/activated carbon; hydrogen In methanol at 30℃; for 0.5h;
1.8
15.2 parts of 2-methyl-6-nitroaniline was dissolved in 300 parts of methanol.The obtained solution was transferred into an autoclave, 2.0 parts of 5% Pd / carbon was added,After reacting at 20 ° C. to 30 ° C. under a hydrogen pressure of 0.2 MPa - 0.5 MPa until hydrogen absorption disappeared, the reaction was further continued at the same temperature for 30 minutes.The catalyst (5% Pd / carbon) was separated by filtration to obtain a solution (filtrate) containing the compound represented by the following formula (22).
With hydrazine hydrate In methanol Reflux;
1
General procedure: In a 250 mL single-necked flask, 0.1 mol of 7-methoxy o-nitroaniline, 40 mL of methanol,75 mL hydrazine hydrate (85%), 0.25 to 0.45 Raney Ni (wet weight), heated to reflux,TCL tracking to the disappearance of raw materials, the reaction after the end of cooling to room temperature, filter to remove Raney Ni,The solvent was removed by distillation under reduced pressure to give a pale brown crystal, i.e., the compound 1 o-phenylenediamine was obtained as shown in Formula 1.In a 250 mL single-necked flask, 0.1 mol of o-phenylenediamine was added, dissolved in 100 mL of ethanol,And then slowly dropping MBF, in the drop process has a yellow solid appears, according to the change of the substituent R1,Reaction time is different at room temperature reaction time period of 30-120min, the reaction is complete,The solvent was removed by filtration, washed three times with ethanol,To give the compound 7-methoxy-2-hydroxy-3-phenylquinoxaline as shown in Formula 2.In the compound 2 by adding 40mLPOCl3 as a solvent, heating under reflux conditions for chlorination,With TLC traced to the disappearance of raw materials, the reaction after the end of cooling to room temperature, slowly into the 500g ice water,A large amount of a yellow solid was immediately precipitated, and the mixture was filtered and washed and dried to obtain Compound 3 as shown in Formula 3.In a 250 mL three-necked flask, compound 3 was added and treated with 60 mL of ethanol as solvent,18 g (0.3 mol) of 85% hydrazine hydrate was slowly added dropwise, and the temperature was raised to reflux after completion of the dropwise addition,The reaction was carried out for 4-5 hours. After completion of the reaction, the mixture was cooled to room temperature, poured into 300 g of ice water, and a large amount of white solid was precipitated by filtration, washed and dried to obtain a crude product which was recrystallized to give compound 4 as shown in Formula 4.To a 50 mL round bottom flask was added 0.377 g (0.002 mol) of hydrazine, 15 mL of ethanol was added as a solvent,Stir under the conditions of slowly dropping 0.002mol substitution aldehydes compounds, the rapid dissolving of raw materials,Followed by solid precipitation, stirring at room temperature overnight, point board monitoring, raw material reaction is complete, the filter,Washed with a mixture of petroleum ether and ethanol three times to give a redish yellow solid powder,I.e., a hydrazone compound containing a methoxybenzopyrazine structure as shown in formula (I).
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; for 6h;
24 g
With palladium 10% on activated carbon; hydrogen In methanol
1.1 Synthesis of 4-methoxypheny-1,2-dilamine
32 g of 5-methoxy-2-nitroaniline was added to 350 ml of methanol, 3.2 g of 10% palladium carbon was added, hydrogen was bubbled in, stirred overnight, filtered, the filtrate was collected, and concentrated to give 24 g of 4-methoxy-1 2-diphenylamine.
With hydrogenchloride; tin(ll) chloride In water at 0 - 20℃; for 1h;
90 %Spectr.
With iron; ammonium chloride In methanol at 80℃; for 24h; Schlenk technique; Inert atmosphere;
3-isopropyl-7-methoxyquinoxalin-2(1H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
79%
With sulfuric acid at 100℃; for 1h;
45%
With acetic acid at 20 - 50℃; Inert atmosphere;
3-Isopropyl-7-methoxyquinoxalin-2(lH)-one (8e)
A mixture of 4-methoxy-l,2-diaminobenzene 4 (130 g, 0.94 mol) and ethyl 3-methyl-2- oxobutanoate 6e (162 g, 1.12 mol) in AcOH (650 mL) was stirred at room temperature overnight, and then heated at 50 °C for 2 h. AcOH was removed under reduced pressure. The residue was diluted with H2O (650 mL) and CH2CI2 (800 mL) and the pH of the mixture was adjusted to pH - 10 by slow addition of 10% aqueous NaOH solution. The resulting precipitate was filtered, washed with CH2CI2 (100 mL) and dried under vacuum to provide the 3-isopropyl-7-methoxyquinoxaline 8e (91 g, 45%) as a light brown solid. NMR (500 MHz, DMSO-de) δ 12.22 (s, 1 H), 7.62 (d, J = 9.0 Hz, 1 H), 6.86 (dd, J = 9.0, 3.0 Hz, 1 H), 6.75 (d, J = 2.5 Hz, 1 H), 3.81 (s, 3H), 3.43-3.37 (m, 1H), 1.19 (d, J = 7.0 Hz, 6 H) ppm;13C NMR (125 MHz, DMSO-6) δ 162.35, 160.36, 154.91, 133.64, 129.90, 126.91, 111.80, 98.24, 55.97, 30.08, 20.57 ppm; MS (ESI) m/z: [M + H]+calcd for C12H15N2O2, 219.26; found 219.50.
Step A: 7-Methoxyquinoxalin-2(1H)-one and 6-methoxyquinoxalin-2(1H)-one A 50% solution of ethyl 2-oxoacetate (18.47 mL, 93 mmol) in toluene was added to a solution of 4-methoxybenzene-1,2-diamine (10.73 g, 78 mmol) in ethanol (100 mL) at ambient temperature and the reaction was refluxed for 2 h. The reaction was concentrated in vacuo and crystallized from ethanol to afford a mixture of 6-methoxyquinoxalin-2(1H)-one and 7-methoxyquinoxalin-2(1H)-one (5.73 g, 32.50 mmol, 42% yield). MS (LC/MS) R.T.=0.68; [M+H]+=177.10.
In ethanol;Reflux;
To a solution of 4-methoxybenzene-1,2-diamine (5 g, 36.2 mmol) in ethanol (50 ml) was added ethyl 2-oxoacetate (4.06 g, 39.8 mmol)). The reaction mass was heated at reflux for overnight. The solvent was evaporated under reduced pressure and the residue was diluted with ethyl acetate and then evaporated to dryness to get the crude compound. The crude compound was washed with pet ether to get crude compound (5.1 g, 80% yield) as a mixture of regioisomers (black solid). This crude compound was taken to the next step without separation of isomers.1H NMR (400 MHz, DMSO-d6): delta ppm 8.17 (s, 1H), 7.98 (s, 1H), 7.70-7.68 (d, J=8 Hz, 1H), 7.31-7.30 (d, J=4 Hz, 1H), 7.27-7.20 (m, 2H), 6.93-6.90 (m, 1H), 6.77-6.76 (d, J=4 Hz, 1H), 3.84 (s, 3H), 3.83 (s, 3H); MS: MS m/z 177.0 (M++1).
In toluene; at 20℃; for 2.0h;Reflux;
50% solution of ethyl2-oxoacetate (18.47 ml., 93mmol) in toluene was added to a solution of 4-methoxybenzene-I,2-diamine (10.73 g, 78 mmol) in ethanol (100 mL) at ambient temperature and the reaction was ref/uxed for 2 h.The reaction was concentrated in vacuo and crystallized fromethanol to afford a mixture of 6-methoxyquinoxalin-2(1H)oneand 7-methoxyquinoxalin-2(1H)-one (5.73 g, 32.50mmol, 42% yield).
In ethanol; toluene; at 0 - 20℃; for 2.0h;
Intermediate 149: 2-Chloro-7-methoxyquinoxalineA solution of 4-methoxybenzene-l,2-diamine (16.8 g, 0.12 mmol) in ethanol (250 mL) was treated with a solution of ethyl oxoacetate (50 wt % in toluene, 50 mL, 0.23 mmol) dropwise with cooling in an ice bath. The reaction was allowed to warm to room temperature and after 2 hours, a precipitate was collected by filtration giving 15 g of a brown solid as a 2:1 mixture of 6-methoxyquinoxalin-2(lH)-one to 7-methoxyquinoxalin-2(lH)-one. These EPO <DP n="135"/>isomers were inseparable by TLC. The mixture was suspended in phosphorus oxychloride (150 niL) and heated to reflux for 1 hour. The reaction was cooled to room temperature and was quenched on ice. The pH of the mixture was adjusted to pH 8 with solid sodium carbonate, it was extracted with ethyl acetate, washed with brine, dried over sodium sulfate, filtered, and concentrated to dryness to give 10.4 g of a crude mixture of 2-chloro-6- methoxyquinoxaline and the desired 2-chloro-7-methoxyquinoxaline. Chromatography on silica gel with 5% ethyl acetate in hexanes afforded 0.77 g of the product as a colorless solid. MS (ESt: 195 (MH+) for C9H7ClN2O1H NMR (CDCht delta 3.96 (s, 3H); 7.29 (d, IH); 7.41 (dd, IH); 7.97 (d, IH); 8.63 (s, IH).
(5-Methoxy-1H-benzimidazole-2-yl)-methanol 26 was prepared using the Phillips procedure [1], 4-Methoxy-1,2-phenylenediamine (0.7 g, 5 mmol) was heated under reflux temperature with glycolic acid (0.4 g, 5.25 mmol) in hydrochloric acid (15 mL, 5.5 M) for 6 h. The reaction mixture was cooled to room temperature and ammonia solution was added and the mixture cooled in ice until a bright brown precipitate formed. The resulting solid was recrystallised from aqueous ethanol to give 5-methoxy-1H-benzimidazole-2-yl)-methanol as a bright brown solid Yield 100%.
A solution of 4-methoxybenzene-1,2-diamine (1.13 g, 8.18 mmol) and hydroxyacetic acid (1.85 g, 24.5 mmol) in 6N hydrochloric acid (25 ml) was heated at reflux for 16 hours. The reaction mixture was cooled to room temperature and neutralised by addition of solid sodium hydroxide. The resulting precipitate was filtered off and dried in vacuo to give the title compound as a pale yellow solid (638 mg).
With hydrogenchloride; In water; for 72h;Heating / reflux;
Compounds 62a & 62b; A solution of 4-methoxy-o-phenylenediamine (5g, 36.1873 mmol), <strong>[1783-96-6]D-aspartic acid</strong> (3.211g, 24.1249 mmol), water (14.6 mL) and concentrated hydrochloric acid (10 ml_) was refluxed for 3 days and then allowed to cool to ambient temperature. The mixture was evaporated to dryness and the regioisomers partially separated by preparative HPLC. LCMS 236 (M+H).
2-[(3,7-Dimethyl-2,6(E)-octadienyl)thio]-5-methoxy-1H-1,3-benzimidazole Monooxalate[ No CAS ]
[ 37052-78-1 ]
Yield
Reaction Conditions
Operation in experiment
63%
With potassium hydroxide; In CS2; ethanol; water;
EXAMPLE 4 2-[(3,7-Dimethyl-2,6(E)-octadienyl)thio]-5-methoxy-1H-1,3-benzimidazole Monooxalate To potassium hydroxide (3.8 g, 0.067M) in ethanol (20 mL) and water (7 mL) was added 2.5 mL CS2 (3.09 g, 0.04M) (H2 S trapped over clorox). The reaction mixture was stirred for 30 minutes at ambient temperature, cooled to 0 C., and 4-methoxy-o-phenylene diamine (5.23 g, 0.03M) was slowly added. This reaction mixture was then stirred at reflux for 4 hours, stirred at ambient temperature overnight (basic soln. with pH paper), evaporated in vacuo and diluted with CH2 Cl2. Addition of water gave a precipitate which was suspended in CH2 Cl2 and acidified to pH 4. Filtration of the suspension gave purple crystalline 5-methoxy-2-mercaptobenzimidazole (3.4 g, 63%).
(16.1) is synthesised, as described in connection with the preparation of (15.3), by using 1,2-dimethoxy-4,5-diaminobenzene, which is prepared from 1,2-dimethoxy-4,5-dinitrobenzene by hydrogenation over 10% Pd/C in methanol, instead of using 1-methoxy-3,4-diaminobenzene. ES(+)-MS: 612 (M+H)+
5-bromo-1H-pyrazolo[3,4-b]pyridine-3-carboxylic acid (2-amino-5-methoxy-phenyl)-amide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
74%
With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 45℃;
A mixture of S-bromo-lEta-pyrazoloCS^-bjpyridine-S-carboxylic acidCompound Ic (200 mg, 0.826 mmol), 4-methoxy-benzehe-l,2-diamine Compound 19a (114 mg, 0.826 mmol), EtaATU (314 mg, 0.826 mmol) and DIPEA (213 mg, 1.652 mmol) in DMF (10 mL) was stirred and heated to 45 C overnight. The mixture was diluted with AeOEt (60 mL) and washed with water. The organic layer was separated, dried and evaporated to give a brown solid residue. The residue was recrystallized with AcOEt/hexane mixture to give 5-bromo-lEta-pyrazolo[3,4-b]pyridine-3-carboxylic acid (2-amin-5-methoxy-phenyl)-amide Compound 19b (221 mg, 74% yield) as a light brown powder. MS m/z 362 (M+).
With triethylamine In N,N-dimethyl-formamide at 0 - 20℃; Inert atmosphere;
3 Example 3
Under nitrogen atmosphere, 10.5 g (76.0 mmol) of 4-methoxy-o-phenylenediamine was dissolved in 200 ml of N, N-(DMF), 31 ml (228 mmol) of triethylamine was added, the mixture was cooled to 0 ° C in ice-water and 10.4 g (50.1 mmol) of 4,5-dichloro-1,2,3-dithiazole Chloride, added after the reaction was continued under nitrogen for 1 hour, then slowly warmed to room temperature and stirred overnight. The reaction mixture was poured into 2 liters of ice water mixture, the solid precipitated, and the solid was collected by suction filtration. The crude product was recrystallized from a 3/1 volume ratio of ethyl acetate / cyclohexane solvent,There was obtained 5.3 g of 2-cyano-6-methoxybenzimidazole as a red-brown solid in a yield of 61%.
With oxygen; triethylamine In toluene at 90℃; for 12h;
4.1. 2-Phenylquinoxaline (3aa)
Typical procedure: Mix Et3N (2.53 mg, 0.025 mmol), 2-phenylacetaldehyde 1a (30 mg, 0.25 mmol), benzene-1,2-diamine 2a (32.4 mg, 0.3 mmol), in toluene (2.5 mL) under O2 (1 atm). The reaction mixture was stirred at 60 °C for 12 h. After cooling down to room temperature and concentrating in vacuum, the residue was purified by flash chromatography on a short silica gel (eluent: petroleum ether/ethyl acetate=20:1) to afford 47 mg (91%) of 3aa.
88%
With [Cu(II)[5,11,17,23-tetrakis(trimethylammonium)-25,26,27,28-tetrahydroxycalix[4]arene](H2O)]I2; oxygen; potassium carbonate In water for 15h; Reflux; Green chemistry;
Typical procedure for one-pot aqueous-phase synthesis of quinoxalines (5a-k) via oxidative cyclization of deoxybenzoins with 1,2-phenylenediamines
A Schlenk tube equipped with a magnetic stirring bar was charged with deoxybenzoin (2a-c, 0.5 mmol), complex 1 (25 mg, 0.025 mmol, 5 mol%), and K2CO3 (7 mg, 0.05 mmol, 5 mol%), which was filled with oxygen gas using an oxygen containing balloon. H2O (3.0 mL) was added to the system via syringe under an oxygen atmosphere. After several minutes' stirring, 1,2-phenylenediamine (4a-l, 0.75 mmol) was added to the reaction system. The mixture was further refluxed for 15 h, which was cooled to roomtemperature and then extracted with CH2Cl2 (3 x 5 mL). The combined organic layer was washed with brine (20 mL) and dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel column
Typical procedure for the condensation synthesis of compound 3a: Benzoin 1a (1.0 equiv.), 1,2-diamine 2a (2.0 equiv.), oxidant (0.35 mol%), and Yb/NaY catalyst (Yb3+ 0.05 equiv.) were reacted in solvent (5 mL) in a 25 mL round bottom flask. The mixture was stirred for 4 h at 80 °C. After completion of the reaction, the mixture was centrifuged and washed with ethyl acetate (3 times 10 mL). The solid catalyst was recovered and dried at 80 °C for 2 h. The combined organic solution was evaporated under reduced pressure and purified by column chromatography on silica gel, eluting with petroleum ether/ethyl acetate (20:1, v/v), to get 2,3-diphenyl-quinoxaline 3a. Other products were synthesized through typical procedures. All 1H NMR results are summarized in Supporting information. The configuration of compounds 3a-3n was assigned by comparing 1H NMR data with known compounds [19-23].
87%
With acetic acid; MORPHIN at 80℃; for 4h;
8
1 mmol of 2-hydroxy-1,2-di-p-tolylethanone , 2 mmol of 4-methoxy-o-phenylenediamine, 0.35 mmol of morphineAnd a Yb / NaY molecular sieve catalyst containing 0.05 mmol Yb3 + were placed in a 25 mL round bottom flask, 5 mLAcetic acid and magnet, stirring at 80 ° C for 4h. The resulting mixture was filtered and the residue was a Yb / NaY molecular sieve, And the filtrate was separated by column chromatography to obtain pure product
(R)-tert-butyl (1-(5-methoxy-1H-benzo[d]imidazol-2-yl)-2-(4-methoxyphenyl)ethyl)carbamate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
( ?)-iert-Butyl (1-(5-methoxy-1 H-benzo[cdimidazol-2-yl)-2-(4- methoxyphenyl)ethyl)carbamate: In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a solution of commercially available (ft)-2-((te/f-butoxycarbonyl)amino)- 3- (4-methoxyphenyl)propanoic acid (500 mg, 1.69 mmol) in AcCN (16.9 mL) was treated at 0 C with 4-ethylmorpholine (0.88 mL, 6.8 mmol), TBTU (544 mg, 1.69 mmol) and 4- methoxybenzene-1 ,2-diamine (234 mg, 1.69 mmol). The reaction mixture was stirred at 0 C for 1 h. The reaction mixture was diluted with EA and water. The org. phase was dried over MgS04, filtered, and the solvent was removed under reduced pressure. The residue was dissolved in glacial acetic acid (16.9 mL) and the reaction mixture was stirred at 60 C for 60 min. The mixture was cooled to rt and the solvent was removed under reduced pressure. The residue was partitioned between EA (30 mL) and sat. aq. NaHC03 (30 mL). The org. layer was washed with sat. aq. NaHC03 (twice 30 mL), dried over MgS04, filtered, and the solvent was removed under reduced pressure. Purification of the residue by combiflash (1 :1 hept-acetone) gave the title compound as yellow solid: TLC: rf (1 : 1 hept-acetone) = 0.48. LC-MS-conditions 07: tR = 0.71 min; [M+H]+ = 398.41.
With lithium hexamethyldisilazane; In tetrahydrofuran; hexane; at 5 - 20℃; for 1.0h;Green chemistry;
General procedure: To a solution of o-aminophenol (400 mg, 3.67 mmol) and NCTS (998 mg, 3.67 mmol) in THF (6 mL), 1 M LiHMDS in hexane (3.67 mL, 3.67 mmol) was added and stirred at 5 °C to r.t. for 1h. Then the reaction mixture was poured in ice water and stirred for 15 min. Then extracted with EtOAc, the organic layer was separated. The organic layer was washed with brine solution.Then organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to obtained pure 2-aminobenzaxozole in 90percent yield (471 mg).
With indium In water at 60℃; for 0.00833333h; Microwave irradiation; Green chemistry; chemoselective reaction;
2.2. General Procedure for the Synthesis ofBenzopyrazines and bis-Benzopyrazines
General procedure: Equimolar ratio of the diamine and dicarbonyl compound(1 mmol scale) was mixed in water (0.5 mL). In case of bisanalog1:2 molar ratio (diamine: dicarbonyl) was taken.Catalytic amount (6 mg, ~5 mol%) of indium powder wasadded and the mixture was placed under microwaveirradiation as described in Tables 2 and 3 and the reactionwas monitored by TLC. After the completion of the reaction,dichloromethane (5 mL) was added to the reaction in twobatches (3 mL and 2 mL) for extraction. The combinedorganic layer was then washed successively with brine (3mL) and water (3 mL). The organic layer was dried withanhydrous sodium sulfate and concentrated. The productswere found to be >95% pure from TLC and 1H-NMR study.Pure products were isolated through crystallization (dichloromethane-hexane). The spectral and analytical datafor all the benzopyrazines and bis-benzopyrazines (Tables 2and 3) are as follows:
With sodium metabisulfite; In N,N-dimethyl-formamide; at 120℃;
General procedure: A solution of substituted o-phenyldiamine (1.0 equiv), thiazole-4-aldehyde or pyridine-2-aldehyde (1.0 equiv) with sodium pyrosulfite in DMF was stirred at 120° C overnight. On completion of the reaction monitored by TLC, the solvent was evaporated and the residue was purified by silica gel chromatography by DCM/MeOH system to afford the final product. If necessary, the crudeproduct could be recrystallized in DCM or dichloroethane to afford pure sample.
With heteropoly-12-tungstophosphoric acid 40% H3[PW12O40]*12H2O supported on graphitic carbon nitride (g-C3N4) In water at 20℃; for 0.5h; Green chemistry;
General procedure for the preparation of quinoxaline derivatives
General procedure: The method for the preparation reported in the literature [22] was followed for the preparation of quinoxaline derivatives. A mixture of 1,2-dicarbonyl compound(1 mmol) and 1,2-diamine (1 mmol) was dissolved in water (5 mL). To this clear solution, catalytic amount (0.03 g) of 40% HPW/g-C3N4-40 was added and the resulting reaction mixture was stirred at room temperature for about 30 min. The progress of the reaction was monitored by TLC using petroleum ether-ethyl acetate(7:3) solvent mixture as eluent. After the completion of the reaction, the reaction mixture was heated. As the product dissolves in ethanol, the catalyst was separated easily from the reaction mixture by simple filtration. The product, obtained by the evaporation of ethanol, was washed several times with water, dried in air oven. By this way, fourteen quinoxaline derivatives were prepared using various substituted1,2-diketones and substituted 1,2-diamines.
With graphene oxide In neat (no solvent) at 60℃; for 3h; Sealed tube; Green chemistry;
S2.1. General procedure for the preparation of quinoxaline derivatives:
General procedure: A mixture of 2-nitro aniline (1 mmol), hydrazine monohydrate (2.2 mmol) and GO (20 mg) was taken in a screw-capped glass tube and stirred the reaction mixture for 3-4 h at 100 °C temperature. After the complete reduction (as monitored by tlc and by the colour change of the reaction mixture from yellow to total black), 1,2-dicarbonyl compound (or α-hydroxy ketone) (1 mmol) was added to the reaction mixture and stirred for few hours at 60 °C (80 °C for α-hydroxy ketone), as mentioned in the Table 2. After completion of the reaction (checked by tlc), the reaction mixture was cooled to room temperature. Water and ethyl acetate were added to the reaction mixture and centrifuge (5000 rpm) the whole reaction mixture to separate the GO (which is now converted to rGO). This process was repeated for three times. The combined organic-aqueous part was then taken in a separating funnel and the organic layer was separated from aqueous layer, and finally dried over anhydrous Na2SO4. Evaporation of the solvent afforded the desired quinoxaline (satisfactorily pure), which was further purified by passing through a short column of silica gel and using the light petroleum ether:ethyl acetate (97:3) as the eluent. All products were characterized by 1H, 13C NMR data and compared with the reported melting points for known solid compounds.
2,3-bis(4-bromophenyl)-6-methoxyquinoxaline[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With graphene oxide; In neat (no solvent); at 60℃; for 3h;Sealed tube; Green chemistry;
General procedure: A mixture of 2-nitro aniline (1 mmol), hydrazine monohydrate (2.2 mmol) and GO (20 mg) was taken in a screw-capped glass tube and stirred the reaction mixture for 3-4 h at 100 C temperature. After the complete reduction (as monitored by tlc and by the colour change of the reaction mixture from yellow to total black), 1,2-dicarbonyl compound (or alpha-hydroxy ketone) (1 mmol) was added to the reaction mixture and stirred for few hours at 60 C (80 C for alpha-hydroxy ketone), as mentioned in the Table 2. After completion of the reaction (checked by tlc), the reaction mixture was cooled to room temperature. Water and ethyl acetate were added to the reaction mixture and centrifuge (5000 rpm) the whole reaction mixture to separate the GO (which is now converted to rGO). This process was repeated for three times. The combined organic-aqueous part was then taken in a separating funnel and the organic layer was separated from aqueous layer, and finally dried over anhydrous Na2SO4. Evaporation of the solvent afforded the desired quinoxaline (satisfactorily pure), which was further purified by passing through a short column of silica gel and using the light petroleum ether:ethyl acetate (97:3) as the eluent. All products were characterized by 1H, 13C NMR data and compared with the reported melting points for known solid compounds.
2-(2,5-dichlorophenyl)-5-methoxy-1H-benzo[d]imidazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
60%
In ethanol; at 80℃; for 4h;
General procedure: ZrO2-Al2O3 solid acid catalytic material was added to the stirred solution of O-phenylenediamines and different substituted aromatic aldehydes in a suitable solvent, and the resulting mixture was heated at a particular temperature and monitored by TLC. After the completion of the reaction, the reaction mixture was cooled and filtered and the residue was washed with ethanol to recover the solid acid catalyst. Filtrate was evaporated in vacuum to get the crude reaction product, which was then purified by silica-gel column chromatography using a suitable mobile phase to separate the desired product. The reaction products were characterized by melting point, 1H NMR and 13C NMR spectroscopy (Bruker, 400 MHz), LC-MS (Varian), and HPLC (Waters) techniques
2-(3,5-dimethylphenyl)-5-methoxy-1H-benzo[d]imidazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
74%
In ethanol; at 80℃; for 2h;
General procedure: ZrO2-Al2O3 solid acid catalytic material was added to the stirred solution of O-phenylenediamines and different substituted aromatic aldehydes in a suitable solvent, and the resulting mixture was heated at a particular temperature and monitored by TLC. After the completion of the reaction, the reaction mixture was cooled and filtered and the residue was washed with ethanol to recover the solid acid catalyst. Filtrate was evaporated in vacuum to get the crude reaction product, which was then purified by silica-gel column chromatography using a suitable mobile phase to separate the desired product. The reaction products were characterized by melting point, 1H NMR and 13C NMR spectroscopy (Bruker, 400 MHz), LC-MS (Varian), and HPLC (Waters) techniques
5-methoxy-2-(4-methoxy-2-methyl-phenyl)-1H-benzo[d]imidazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
80%
In ethanol at 80℃; for 8h;
Catalytic activity studies of solid acid catalytic materials in the synthesis of benzimidazoles
General procedure: ZrO2-Al2O3 solid acid catalytic material was added to the stirred solution of O-phenylenediamines and different substituted aromatic aldehydes in a suitable solvent, and the resulting mixture was heated at a particular temperature and monitored by TLC. After the completion of the reaction, the reaction mixture was cooled and filtered and the residue was washed with ethanol to recover the solid acid catalyst. Filtrate was evaporated in vacuum to get the crude reaction product, which was then purified by silica-gel column chromatography using a suitable mobile phase to separate the desired product. The reaction products were characterized by melting point, 1H NMR and 13C NMR spectroscopy (Bruker, 400 MHz), LC-MS (Varian), and HPLC (Waters) techniques
2-(4-fluoro-2-(trifluoromethyl)phenyl)-5-methoxy-1H-benzo[d]imidazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
84%
In ethanol; at 80℃; for 4h;
General procedure: ZrO2-Al2O3 solid acid catalytic material was added to the stirred solution of O-phenylenediamines and different substituted aromatic aldehydes in a suitable solvent, and the resulting mixture was heated at a particular temperature and monitored by TLC. After the completion of the reaction, the reaction mixture was cooled and filtered and the residue was washed with ethanol to recover the solid acid catalyst. Filtrate was evaporated in vacuum to get the crude reaction product, which was then purified by silica-gel column chromatography using a suitable mobile phase to separate the desired product. The reaction products were characterized by melting point, 1H NMR and 13C NMR spectroscopy (Bruker, 400 MHz), LC-MS (Varian), and HPLC (Waters) techniques
With cesiumhydroxide monohydrate In toluene at 150℃; for 24h; Inert atmosphere; Sealed tube;
2.2 Quinoxaline synthesis from diamine
General procedure: To an oven dried 9mL screw cap tube, a magnetic stir-bar, diamine (0.5mmol), vicinal diol (1.5mmol), CsOH.H2O (0.375mmol), Co-phen/C-800 (1.5mol%) and toluene (2.5mL) were added under argon atmosphere. Then, the tube was sealed and placed in a preheated oil bath at 150°C for 24h. After completion of the reaction, the tube was allowed to cool at room temperature. Then, the solvent was evaporated under reduced pressure. Finally, the product was purified by silica gel column chromatography using ethyl acetate/hexane as eluent.
84%
With C18H24ClIrN3O(1+)*Cl(1-); potassium hydroxide In water for 24h; Schlenk technique; Reflux; Green chemistry;
66%
With C24H29IrN2O5(2+)*2CF3O3S(1-); caesium carbonate In 5,5-dimethyl-1,3-cyclohexadiene at 150℃; for 48h; Schlenk technique; Inert atmosphere;
General procedure for the synthesis of 3a.
General procedure: The catalyst A (5% mmol, 0.05 mmol), 1,2-phenylenediamine (1 mmol, 1.0 equiv), 1,2-propanediol (1 mmol, 1.0 equiv), Cs2CO3 (3.0 equiv) and xylene (4 mL) were added to a Schlenk tube under the atmosphere of nitrogen. The mixture was heated for 48 h at 150 °C and then cooled down to room temperature. The volatile solvent was evaporated. The residue was purified by column chromatography to give the corresponding product 3a.
1-(2-((2-amino-4-methoxyphenyl)amino)pyridin-3-yl)ethan-1-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In 1,4-dioxane; at 100℃;
Step 1: A mixture of 4-methoxybenzene-1,2-diamine (2.0g, 14.48mmol) and 1-(2-fluoropyridin- 3-yl)ethanone (2.01g, 14.48mmol) in dioxane (20mL) was heated at 100C overnight. The reaction mixture was cooled to RT. The solvent was removed under reduced pressure, and the crude was purified by ISCO silica gel chromatography using hexane and ethyl acetate (0-100%) to afford 1-(2-((2-amino-4-methoxyphenyl)amino)pyridin-3-yl)ethan-1-one as an oil. MS: 258 (M+1).
(Z)-3-(2-(4-chlorophenyl)-2-oxoethylidene)-6-methoxy-3,4-dihydroquinoxalin-2(1H)-one[ No CAS ]
(Z)-3-(2-(4-chlorophenyl)-2-oxoethylidene)-7-methoxy-3,4-dihydroquinoxalin-2(1H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
46%
With Methyl p-tolyl sulfone; In N,N-dimethyl-formamide; at 20℃; for 72h;Inert atmosphere;
General procedure: A solution of <strong>[5814-38-0]ethyl 4-chlorobenzoylpyruvate</strong> 100 mg (0.39 mmol, 1.00 equiv) 12a, o-phenylenediamine (1.00 equiv) from 11a-f with or without an additive (1.00 equiv) (p-TsOH or DMAP) was stirred in 3.0 ml of DMF (abs) at rt under Ar for 72 h. A low soluble mixtureof ANTI/SYN regioisomers slowly precipitated within the reaction. The precipitate was collected by filtration or centrifugation, triturated by 3 ml of Et2O and crystallized from DMSO (if not otherwise stated) to yield the main solid regioisomer 16 or 17.
General procedure: To a 10mL three-necked round bottle was charged with 1a (0.54 g, 5 mmol), imidazolium chloride (0.09 g, 0.5 mmol) and N,N-dimethylformamide 2 mL. The resulting solution was warmed to120 C and stirred at this temperature for 6 h. When the reaction was completed, 25 mL water was added and the resulting mixture was extracted with 25 mL ethyl acetate twice. The combined organic layer was successively washed with H2O (50 mL) and then brine (50 mL), then dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel with petroleum ether and ethyl acetate or recrystallized from petroleum ether/EA to give the title products.
A mixture of 4-methoxy-l,2-diaminobenzene 4 (5.0 g, 36.2 mmol) and ethyl 2- oxobutanoate 6a (5.70 g, 43.8 mmol) in AcOH (25 mL) was stirred at room temperature overnight and then heated at 50 C for 2 h. AcOH was removed under reduced pressure, and the reside was extracted with CH2CI2 (2chi150 mL). The combined organic portions were washed with H2O and 10% aqueous Na2C03 solution, dried (Na2S04), and evaporated under reduced pressure. The residue was triturated with hexanes and filtered. The solid was mixed with EtOAc (25 mL), stirred at room temperature for 30 min, filtered, and dried under high vacuum to provide the 3-ethyl-7- methoxyquinoxaline 8a (6.0 g, 81%) as a light purple solid. NMR (500 MHz, DMSO- e) delta 12.17 (s, 1 H), 7.61 (d, J= 8.5 Hz, 1 H), 6.85 (dd, J= 9.0, 2.5 Hz, 1 H), 6.73 (d, J= 2.5 Hz, 1 H), 3.80 (s, 3 H), 2.74 (q, J= 7.5 Hz, 3 H), 1.19 (t, J= 7.5 Hz, 3 H) ppm;13C NMR (125 MHz, DMSO- e) delta 160.30, 159.35, 155.26, 133.63, 129.78, 127.01, 111.78, 98.26, 55.97, 26.17, 10.08 ppm; MS (ESI) m/z: [M + H]+calcd for C11H13N2O2, 205.24; found 205.90.
With sodium hydrogencarbonate; In N,N-dimethyl acetamide; at 80℃;
General procedure: 1,2-Dibromoethane (2.1 mL, 24 mmol) was added dropwise to a suspension of substituted ophenylenediamine derivative 1 (20 mmol) and NaHCO3(16.8g, 200 mmol) in dimethyl acetylamide (30mL) at 800 while stirring for 6-8 hr. The reaction mixture was cooled, filtered, washed thoroughly with NaCl aq, and dried over anhydrous Na2SO4. After concentration under reduced pressure, the residue was subjected to silica gel chromatography eluting with EtOAc-petroleum ether (PE) mixture (4:1) to get 2a-f.
General procedure: In a 50 mL three-necked flask, 4-methoxy-o-phenylenediamine 1a (1.0 g, 7.24 mmol, 1.0 eq) and methanol 15 mL were added, and it was completely dissolved under stirring. Next, triethylamine (3.66g, 36.2mmol, 5.0eq) was added under nitrogen protection and stirred for 10 minutes, followed by slowly adding ethyl 2-oxo-5-hexenoate 2a (1.35g, 8.68mmol, 1.2eq), The reaction was stirred at room temperature for 8 hours. Extracted twice with ethyl acetate, washed the organic phase twice with saturated ammonium chloride solution, then washed twice with brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, purified to obtain the mixing point of the two products, yield 76%, HPLC detection The regioisomer 3a / 4a ratio is 3.9: 1.
4-(5-methoxy-1H-benzo[d]imidazol-2-yl)butan-1-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
91%
With hydrogenchloride In water for 12h; Reflux; Sealed tube;
General Conditions A:
General procedure: A mixture of the corresponding orthophenylenediamine(1 equiv) and the corresponding lactone orlactam (4-6 equiv) in 4N HCl in a sealed tube was heated overnight(duration is reported in the manuscript). After cooling toroom temperature, the pH was adjusted to pH 11 at 0 °C withsat. aq. K2CO3. The aqueous layer was extracted three times withEtOAc, the combined organic layers were washed with brine,dried over MgSO4, filtered, and concentrated in vacuo. Thedesired product was obtained by precipitation or by chromatographyon silica gel [eluting with CH2Cl2-MeOH/ammonia, 9:1(v/v)]. The final solid or oil obtained was dried over P2O5.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
HazMat Fee +
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
