* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With hydrogenchloride In water at 0 - 20℃; for 2 h;
Concentrated hydrochloric acid (4.16 mL, 49.9 mmol) was added to a mixture of commercially available 2-amino-5-methylbenzamide 14 (5.00 g, 33.3 mmol) and trimethyl orthoformate (51.0 mL, 466 mmol) at 0 °C and the mixture was stirred at room temperature for 2 h. After the mixture was concentrated under reduced pressure, the residue was diluted with water and neutralized with 2 M aqueous sodium hydroxide solution. The precipitated solid was collected and washed with H2O, methanol and diethyl ether to give 15 as a white powder (4.33 g, 81percent). 1H NMR (300 MHz, DMSO-d6) d 2.44 (3H, s), 7.57 (1H, d, J = 8.4 Hz), 7.62–7.66 (1H, m), 7.91–7.93 (1H, m), 8.03 (1H, s), 12.2 (1H, bs).
Reference：
[1] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 19, p. 5487 - 5505
[2] Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 4, p. 545 - 548
[3] Bioorganic and Medicinal Chemistry, 2003, vol. 11, # 3, p. 383 - 391
2
[ 67-56-1 ]
[ 40545-33-3 ]
[ 19181-53-4 ]
Yield
Reaction Conditions
Operation in experiment
90%
at 130℃; for 2 h; Inert atmosphere; Microwave irradiation
2-amino-5-methylbenzamide (75 mg, 0.5 mmol), [Cp * Ir (2,2'-bpyO) (H2O)](5.4 mg, 0.005 mmol, 1 molpercent),Cesium carbonate (49 mg, 0.15 mmol, 0.3 equiv.) And methanol (0.5 ml) were sequentially added to a dried 5 mL microwave reaction tube.Microwave tube nitrogen protection,Placed in a single mode pressure microwave synthesizer (Discover CEM,USA). After the reaction mixture was reacted at 130 ° C for 2 hours,Cool to room temperature. Rotary evaporation to remove the solvent,Then, column chromatography (developing solvent: petroleum ether / ethyl acetate)The pure target compound was obtained in a yield of 90percent
Reference：
[1] Organic Letters, 2016, vol. 18, # 11, p. 2580 - 2583
[2] Patent: CN107337646, 2017, A, . Location in patent: Paragraph 0035; 0036; 0037; 0038
3
[ 40545-33-3 ]
[ 58421-79-7 ]
Reference：
[1] Bioorganic and Medicinal Chemistry, 2003, vol. 11, # 3, p. 383 - 391
[2] Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 4, p. 545 - 548
4
[ 40545-33-3 ]
[ 123-54-6 ]
[ 18731-19-6 ]
Reference：
[1] Journal of Organic Chemistry, 2015, vol. 80, # 19, p. 9392 - 9400
5
[ 4315-12-2 ]
[ 40545-33-3 ]
Yield
Reaction Conditions
Operation in experiment
99%
With hydrogen In methanol at 20℃; for 12 h;
Step 2 To a solution of 5-methyl-2-nitrobenzamide (15.0 g, 83.3 mmol) in methanol (300 mL) was added 10percent palladium carbon (2.50 g), and the mixture was stirred at room temperature for 12 hr under hydrogen atmosphere (1 atm). The insoluble material was filtered off, and the filtrate was concentrated to give 2-amino-5-methylbenzamide as a white powder (12.4 g, 99percent).
99%
With palladium 10% on activated carbon; hydrogen In methanol at 10 - 35℃; for 12 h;
Step 2 To a solution of 5-methyl-2-nitrobenzamide (15.0 g, 83.3 mmol) in MeOH (300 mL) was added 10percent Pd-C (2.50 g), and the mixture was stirred under a hydrogen atmosphere (1 atm) at room temperature for 12 hrs. Insoluble material was filtered off and the filtrate was concentrated to give 2-amino-5-methylbenzamide as a white powder (12.4 g, 99percent).
96%
With H2 In methanol
A solution of 13 (31.5 g, 0.175 mol) in MeOH (250 mL) was shaken With 5percent Pd-C (0.5 g) under 3 atm. of H2 for 24 h in a Parr apparatus. A solid formed after the initial heat of reaction subsided. The mixture was heated to boiling to redissolve the product, and was filtered while hot. The filtrate was evaporated under reduced pressure and the residue dried at 90° C. for 1 h (caution: some sublimation may occur) to obtain 2-amino-5-methylbenzamide (14) as a white solid (25.3 g, 96percent); mp 173°-175° C. [lit. (Findeklee) mp 179° C.]; 1 H-NMR (CDCl3) δ6.60 (d, 1H, J=8 Hz, C3 -H).
Reference：
[1] Patent: EP1953148, 2008, A1, . Location in patent: Page/Page column 130
[2] Patent: US2015/329556, 2015, A1, . Location in patent: Paragraph 1532
[3] Journal of Medicinal Chemistry, 1992, vol. 35, # 14, p. 2626 - 2630
[4] Patent: US5234925, 1993, A,
[5] European Journal of Medicinal Chemistry, 2011, vol. 46, # 7, p. 2786 - 2796
[6] European Journal of Medicinal Chemistry, 2013, vol. 65, p. 427 - 435
[7] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 19, p. 6305 - 6316
[8] European Journal of Medicinal Chemistry, 2017, vol. 132, p. 262 - 273
6
[ 2941-78-8 ]
[ 40545-33-3 ]
Yield
Reaction Conditions
Operation in experiment
74%
Stage #1: With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide for 3 h; Inert atmosphere Stage #2: With ammonium hydroxide In water; N,N-dimethyl-formamide for 16 h;
Compound 23 (3.00 g , 19.78 mmol) was treated withEDC.HCl (4.17 g, 21.8 mmol) and HOBt (3.33 g, 21.8 mmol) in dry DMF (100 mL) under Arfor 3 h, after which aq. NH3 (35percent, 20 mL) was added and the mixture was stirred for 16 h.The evaporation residue, in EtOAc, was and washed twice with water and with brine. Dryingand evaporation gave 26 as an off-white solid (2.21 g, 74percent): mp 180-182°C (lit.S13 mp 175-177°C); 1H NMR ((CD3)2SO) 2.20 (3 H, s, Me), 6.35 (2 H, brs, NH2), 6.64 (1 H, d, J = 8.3Hz, 3-H), 7.01 (2 H, m, 4-H + CONHH), 7.40 (1 H, d, J = 1.2 Hz, 6-H), 7.68 (1 H, s,CONHH); 13C NMR ((CD3)2SO) (HSQC / HMBC) 19.98 (Me), 113.78 (1-C), 116.52 (3-C),122.68 (5-C), 128.64 (6-C), 132.67 (4-C), 147.84 (2-C), 171.27 (C=O).
70%
With N-hydroxybenzotriazole ammonium salt; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 1 h;
To a stirred solution of 2-amino-5-methyl-benzoic acid (100 mg, 0.66 mmol) in THF (2 mL),EDC.HCl (189 mg, 0.99 mmol), HOBt·NH3 (149 mg, 0.99 mmol) and DIPEA (0.35 mL, 1.99mmol) were added at RT and stirred for 1 h (TLC indicated complete conversion of thestarting material). The reaction mixture was diluted with EtOAc (1 x 50 mL), washed withwater (1 x 20 mL) and brine solution (1 x 20 mL). The organic layer was separated, dried over Na2S04, volatiles were evaporated under reduced pressure to give the crude residuewhich was purified by Combiflash Rf 200 Teledyne ISCO (100percent EtOAc, 12 gm cartridge) toafford 2-amino-5-methyl-benzamide (70 mg, 70percent) as a white solid.LCMS (ESI+): m/z: 151.13 [M+Ht.
Reference：
[1] European Journal of Medicinal Chemistry, 2016, vol. 118, p. 316 - 327
[2] Journal of Organic Chemistry, 2017, vol. 82, # 14, p. 7165 - 7175
[3] Patent: WO2018/125961, 2018, A1, . Location in patent: Page/Page column 51; 52
[4] Organic Letters, 2013, vol. 15, # 2, p. 378 - 381
[5] Bioorganic and Medicinal Chemistry, 2003, vol. 11, # 3, p. 383 - 391
[6] Journal of Agricultural and Food Chemistry, 2015, vol. 63, # 31, p. 6883 - 6889
7
[ 5925-93-9 ]
[ 40545-33-3 ]
Yield
Reaction Conditions
Operation in experiment
90%
With water; potassium carbonate In water at 150℃; for 0.5 h; Microwave irradiation
General procedure: Adapted from a literature procedure,1 the appropriate organonitrile (1.0 eq.) and K2CO3(0.2eq.)wereaddedtoamicrowavetubewithastir-barwithdeionizedwater(8.5mLpermmolsubstrate).Afterirradiationundermicrowaveat150°Cfor30minutes,thereactionmixturewascooled,extractedwithEtOAc(320mL),thecombinedphasesdriedoverMgSO4andexcesssolventremovedinvacuo.TheresiduewaspurifiedbyFCC,ifrequired,togivethetitlecompound.
With ammonia In tetrahydrofuran; methanol; N,N-dimethyl-formamide
28a 2-Amino-5-methylbenzamide To a stirred solution of 5-methyl-2-nitrobenzoic acid (25.4 g) in THF (150 ml) was added oxalyl chloride (13.5 ml) and DMF (0.1 ml) dropwise and the mixture was stirred at room temperature for 14 hours and concentrated to dryness. To an ice-cooled, stirred 25percent aqueous solution of ammonia (150 ml) was added the resulting acid chloride dropwise and the mixture was stirred at the same temperature for 1 hour. The white precipitates were collected by filtration, washed with water, and dried in vacuo. A suspension of the white precipitates and 10percent Pd/C (2.4 g) in a mixture of THF (200 ml) and methanol (150 ml) was stirred under hydrogen atmosphere at room temperature for 4 hours. After removal of insoluble materials by filtration, the filtrate was concentrated to dryness. Recrystallization of the resultant crystalline residue from ethyl acetate-hexane afforded colorless crystals (18.7 g, 89percent), m.p. 178°-180° C. 1 H-NMR(200 MHz,DMSO-d6) δ: 2.15(3H,s), 6.30(2H,brs), 6.58(1H,d), 6.95(1H,dd), 6.97(1H,br), 7.34(1H,d), 7.64(1H,br) IR(KBr) cm-1: 3380, 3200, 1645, 1580, 1552
Reference：
[1] Patent: US5389641, 1995, A,
9
[ 3113-72-2 ]
[ 40545-33-3 ]
Reference：
[1] Journal of Medicinal Chemistry, 1992, vol. 35, # 14, p. 2626 - 2630
[2] European Journal of Medicinal Chemistry, 2011, vol. 46, # 7, p. 2786 - 2796
[3] European Journal of Medicinal Chemistry, 2013, vol. 65, p. 427 - 435
[4] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 19, p. 6305 - 6316
[5] European Journal of Medicinal Chemistry, 2017, vol. 132, p. 262 - 273
[6] Patent: US2015/329556, 2015, A1,
10
[ 2941-78-8 ]
[ 530-62-1 ]
[ 40545-33-3 ]
Reference：
[1] Patent: US5001157, 1991, A,
11
[ 4692-99-3 ]
[ 40545-33-3 ]
Reference：
[1] Journal of Chemical Research, Miniprint, 1987, # 7, p. 1839 - 1868
[2] Journal of Agricultural and Food Chemistry, 2015, vol. 63, # 31, p. 6883 - 6889
12
[ 38818-49-4 ]
[ 40545-33-3 ]
Reference：
[1] European Journal of Medicinal Chemistry, 2013, vol. 65, p. 427 - 435
[2] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 19, p. 6305 - 6316
[3] European Journal of Medicinal Chemistry, 2017, vol. 132, p. 262 - 273
[4] Patent: US2015/329556, 2015, A1,
13
[ 64113-86-6 ]
[ 40545-33-3 ]
Reference：
[1] Chemische Berichte, 1905, vol. 38, p. 3555
14
[ 620-22-4 ]
[ 40545-33-3 ]
Reference：
[1] Chemische Berichte, 1905, vol. 38, p. 3555
With hydrogen;palladium 10% on activated carbon; In methanol; at 20℃; under 760.051 Torr; for 12h;
Step 2 To a solution of 5-methyl-2-nitrobenzamide (15.0 g, 83.3 mmol) in methanol (300 mL) was added 10% palladium carbon (2.50 g), and the mixture was stirred at room temperature for 12 hr under hydrogen atmosphere (1 atm). The insoluble material was filtered off, and the filtrate was concentrated to give 2-amino-5-methylbenzamide as a white powder (12.4 g, 99%).
99%
With palladium 10% on activated carbon; hydrogen; In methanol; at 10 - 35℃; under 760.051 Torr; for 12h;
Step 2 To a solution of 5-methyl-2-nitrobenzamide (15.0 g, 83.3 mmol) in MeOH (300 mL) was added 10% Pd-C (2.50 g), and the mixture was stirred under a hydrogen atmosphere (1 atm) at room temperature for 12 hrs. Insoluble material was filtered off and the filtrate was concentrated to give 2-amino-5-methylbenzamide as a white powder (12.4 g, 99%).
96%
With H2;Pd-C; In methanol;
A solution of 13 (31.5 g, 0.175 mol) in MeOH (250 mL) was shaken With 5% Pd-C (0.5 g) under 3 atm. of H2 for 24 h in a Parr apparatus. A solid formed after the initial heat of reaction subsided. The mixture was heated to boiling to redissolve the product, and was filtered while hot. The filtrate was evaporated under reduced pressure and the residue dried at 90 C. for 1 h (caution: some sublimation may occur) to obtain 2-amino-5-methylbenzamide (14) as a white solid (25.3 g, 96%); mp 173-175 C. [lit. (Findeklee) mp 179 C.]; 1 H-NMR (CDCl3) delta6.60 (d, 1H, J=8 Hz, C3 -H).
With hydrogenchloride; tin(ll) chloride; In water; at 0 - 5℃; for 24h;
To a magnetically stirred suspension of stannous chloride (0.038 mol) in concentrated HCl (37%) (15 ml), 0.013 mole of 7a was added at a rate so that the temperature of the slurry was maintained below 5 C (about 1 h). After addition was complete, the mixture was stirred for 24 h. The white slurry thus obtained was diluted with cold water (150 ml), and aqueous sodium hydroxide (40%) was added until the tin salt dissolved. The solution was extracted with ethyl acetate (3 × 150 ml), and the extracts dried and evaporated in vacuo to obtain pure 10a.
With hydrogenchloride; tin(ll) chloride; at 5℃; for 25h;
General procedure: To a magnetically stirred suspension of stannous chloride (0.038 mol) in concentrated HCl (37%), 0.013 mol of 7a-c was added (15 ml) at a rate so that the temperature of the slurry was maintained below 5 C (about 1 h). After addition was complete, the mixture was stirred for 24 h. The white slurry thus obtained was diluted with cold water (150 ml), and sodium hydroxide (40%) was added until the tin salt dissolved. The solution was extracted with ethyl acetate (3 150 ml), and the extracts dried and evaporated in vacuo to obtain pure 2d,f,g.
With hydrogenchloride; tin(ll) chloride; at 5℃; for 25h;
General procedure: To a magnetically stirred suspension of stannous chloride (0.038 mol) in concentrated HCl (37%), 0.013 mol of 13a-c was added (15 mL) at a rate so that the temperature of the slurry was maintained below 5 C (about 1 h). After addition was complete,the mixture was stirred for 24 h. The white slurry thus obtained was diluted with cold water (150 mL), and NaOH (40%) was added until the tin salt dissolved. The solution was extracted with ethylacetate (3 150 mL), and the extracts dried and evaporated to obtain pure 15d,e,f.
Example 2A 6-Methyl-1,2,3-benzotriazin-4(3H)-one To a suspension of 32.0 g (213.08 mmol) of <strong>[40545-33-3]2-amino-5-methylbenzamide</strong> in 300 ml of a 2:1 mixture of water and conc. hydrochloric acid at 0 C. was gradually added a solution of 16.17 g (234.38 mmol) of sodium nitrite in 120 ml of water, in the course of which the internal temperature was kept below 5 C. After stirring at bath temperature 0 C. for 30 minutes, while continuing to cool with an ice bath, 120 ml (1.2 mol) of 10 M sodium hydroxide solution were added, in the course of which the internal temperature rose to about 20 C. and solids that were present went into solution. After stirring at RT for 1 h, the mixture was cautiously acidified with conc. hydrochloric acid (pH=2). The precipitate formed was filtered off and washed three times with water. After drying under air and under reduced pressure, 33.80 g (98% of theory) of the title compound were obtained. 1H-NMR (400 MHz, DMSO-d6): delta [ppm]=14.85 (br. s, 1H), 8.08 (d, 1H), 8.02 (s, 1H), 7.90 (d, 1H). LC/MS (Method 3, ESIpos): Rt=1.40 min, m/z=162 [M+H]+.
98%
With hydrogenchloride; sodium hydroxide; sodium nitrite; In water; at 0 - 5℃; for 0.5h;
To a suspension of 32.0 g (213.08 mmol) of <strong>[40545-33-3]2-amino-5-methylbenzamide</strong> in 300 ml of a 2:1 mixture of water and conc. hydrochloric acid at 0C. was gradually added a solution of 16.17 g (234.38 mmol) of sodium nitrite in 120 ml of water, in the course of which the internal temperature was kept below 5C. After stirring at bath temperature 0C. for 30 minutes, while continuing to cool with an ice bath, 120 ml (1.2 mol) of 10 M sodium hydroxide solution were added, in the course of which the internal temperature rose to about 20C. and solids that were present went into solution. After stirring at RT for 1 h, the mixture was cautiously acidified with conc. hydrochloric acid (pH=2). The precipitate formed was filtered off and washed three times with water. After drying under air and under reduced pressure, 33.80 g (98% of theory) of the title compound were obtained. [0327] 1H-NMR (400 MHz, DMSO-d6): delta [ppm]=14.85 (br. s, 1H), 8.08 (d, 1H), 8.02 (s, 1H), 7.90 (d, 1H). [0328] LC/MS (Method 3, ESIpos): Rt=1.40 min, m/z=162 [M+H]+.
97%
With sodium hydroxide; sodium nitrite; In hydrogenchloride; water;
To an ice-cold suspension of 14 (25.3 g, 0.168 mol) in 3.6N HCl (260 mL) was added dropwise over 25 min a solution of NaNO2 (12.75 g) in H2 O (100 mL) while keeping the internal temperature below 5 C. After another 20 min of stirring at this temperature, 10N NaOH (100 mL) was added, causing all the solid to dissolve. The solution was acidified to pH 2 with 12N HCl and chilled. The solid was filtered and recrystallized from EtOH to obtain off-white needles (26.2 g, 97%); mp 217-218 C. (dec, gas evolution) [lit. (Ferrand et al., Eur. J. Med. Chem. 2:337, 1987) mp 219-220 C.]; IR (KBr) v 1680 (lactam C=O); 1 H--NMR (d6 --DMSO+D2 O) delta3.30 (s, 3H, 6--Me), 8.00 (m, 3H, aryl); UV (95% EtOH) lambdamax 208, 225, 282 nm.
63%
A suspension of <strong>[40545-33-3]2-amino-5-methylbenzamide</strong> (500 mg, 3.3 mmol) in HCl (2N, 5 mL) at 0 C was treated with NaNO2 (252 mg, 3.7 mmol) for 1.25 h. The suspension was then filtered. The filtrate was made basic with Na2CO3 (20 % soln) and the resulting solid collected via vacuum filtration to provide 334.7 mg (63 %) of the title compound as a white solid. 1H NMR (DMSO-J6) delta 8.06 - 8.11 (m, 1 H), 8.05 (d, 1 H), 7.87 - 7.91 (m, 1 H) 2.59 (s, 3 H). HRMS (ES) calcd for C8H8N3O (M + H) 162.0662, found 162.0660.
With hydrogenchloride; sodium nitrite; In water; N,N-dimethyl-formamide; at 0℃; for 1h;
General procedure: Intermediates 2a-h were preparedby the similar method described in the literature [1] (Scheme 1). At 0 C, to a solution of sodium nitrite (1.38 g, 20 mmol) in 0.5 M hydrochloric acid (80 mL) was added anthranilamide 1 (10 mmol) in DMF (8 mL) over a period of 30 min. After that, the above mixture was stirred for another 1 h at 0 C. Then the mixture was basified with 30% aqueous ammonia and reacidified with hydrochloric acid to pH 2.0. The precipitate was filtered off with suction, washed with water and dried to afford the crude product, which was finally recrystallized from ethanol to yield 2.
General procedure: A solution of anthranilamide (I, 30 mmol) in DMF (15 mL) was added dropwise to a well-stirred solution of sodium nitrite (4.14 g, 60 mmol) in 0.5 M HCl (240 mL) at 0 C over a period of 40 min. After the stirring was continued at 0-5 C for 1 h, 30% aqueous ammonia was added slowly to adjust the pH to 10.0, and then reacidified to pH 2.0. After vigorously stirring for 30 min, the mixture was filtered with suction, and the filter cake was washed with water (200 mL) and dried to afford 1,2,3-benzotriazin-4-one II in yields of above 80%.
With hydrogenchloride; In water; at 0 - 20℃; for 2h;
Concentrated hydrochloric acid (4.16 mL, 49.9 mmol) was added to a mixture of commercially available 2-amino-5-methylbenzamide 14 (5.00 g, 33.3 mmol) and trimethyl orthoformate (51.0 mL, 466 mmol) at 0 C and the mixture was stirred at room temperature for 2 h. After the mixture was concentrated under reduced pressure, the residue was diluted with water and neutralized with 2 M aqueous sodium hydroxide solution. The precipitated solid was collected and washed with H2O, methanol and diethyl ether to give 15 as a white powder (4.33 g, 81%). 1H NMR (300 MHz, DMSO-d6) d 2.44 (3H, s), 7.57 (1H, d, J = 8.4 Hz), 7.62-7.66 (1H, m), 7.91-7.93 (1H, m), 8.03 (1H, s), 12.2 (1H, bs).
Dimethyl N-[4-(1,2,3-Benzotriazin-4(3H)-on-6-yl) methyl]aminobenzoyl-L-glutamate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In glacial AcOH;
Dimethyl N-[4-(1,2,3-Benzotriazin-4(3H)-on-6-yl) methyl]aminobenzoyl-L-glutamate (22). N-Bromosuccinimide (1.37 g, 7.7 mmol) was added in a single portion to a solution of 14 (1.13 g, 7 mmol) in glacial AcOH (70 mL) in an oil bath at 60 C. The resulting solution was heated at 70 C. with illumination from a 150-watt floodlamp (General Electric) for 2 h. After evaporation of the solvent under reduced pressure, the residue was partitioned between CHCl3 and H2 O. The CHCl3 layer was washed with 5% NaHCO3, rinsed with H2 O, and evaporated to obtain a product (0.946 g) which was estimated to consist of a 2:3 mixture of 6-bromomethyl-1,2,3-benzotriazin-4(3H)-one (20) [1 H--NMR (CDCl3) delta4.63] and unchanged 15 [1 H--NMR (CDCl3) delta3.30]. The entire mixture of 20 and 15 from the bromination reaction (estimated to contain 1.97 mmol of 20 from the delta4.63/delta3.30 ratio) was added in a single portion to a solution of dimethyl N-(4-aminobenzoyl)-L-glutamate (0.588 g, 2 mmol) (Koehler et al., J. Amer. Chem. Soc., 80:5779, 1958) in dry DMF (10 mL). Then, solid NaHCO3 (0.168 g, 2 mmol) was added and the mixture was kept in an oil bath at 65 C. for 3 days. The solvent was evaporated under reduced pressure and the residue partitioned between CHCl3 and H2 O. The CHCl3 layer (TLC: Rf 0.70, 0.65, 0.4, 0.0; silica gel, 19:1 CHCl3 -MeOH) was evaporated and the residue chromatographed on a silica gel column (45 g, 2.5*40 cm) with 20:1 CHCl3 --MeOH as the eluent. Pooled fractions containing the spot with Rf =0.4 were evaporated in two batches, and the residues were dried separately in vacuo (P2 O5, 65 C.). The first batch (0.254 g, 28%) was TLC-homogeneous, whereas the other (0.154 g, 17%) contained a small impurity. Rechromatography of the TLC-homogeneous batch afforded analytically pure 10 as a beige powder (0.22 g, 87% recovery)); mp 94-102 C.; IR (KBr) v 3430, 3040, 2960, 1740, 1690, 1640, 1615, 1580, 1515, 1445, 1420, 1335, 1285, 1265 cm-1; NMR (CDCl3) delta1.71 (br s, 1H, lactim OH), 2.43 (m, 4H, CH2 CH2), 3.63 (s, 3H 65 -COOMe), 3.75 (s, 3H, alpha-COOMe), 4.65 (m, 4H, CH2 N, NH, alpha-CH), 6.58 (d, J=9 Hz, 2H, 3'- and 5'-H), 7.68 (d, J=9 Hz, 2H, 2'- and 6'- H), 7.8-8.4 (m, 3H, aryl). Anal. Calcd for C22 H23 N5 O6.0.6H2 O: C, 56.92; H, 5.25; N, 15.08. Found: C, 57.05; H, 5.00; N, 14.71.
With ammonia;palladium-carbon; In tetrahydrofuran; methanol; N,N-dimethyl-formamide;
28a 2-Amino-5-methylbenzamide To a stirred solution of 5-methyl-2-nitrobenzoic acid (25.4 g) in THF (150 ml) was added oxalyl chloride (13.5 ml) and DMF (0.1 ml) dropwise and the mixture was stirred at room temperature for 14 hours and concentrated to dryness. To an ice-cooled, stirred 25% aqueous solution of ammonia (150 ml) was added the resulting acid chloride dropwise and the mixture was stirred at the same temperature for 1 hour. The white precipitates were collected by filtration, washed with water, and dried in vacuo. A suspension of the white precipitates and 10% Pd/C (2.4 g) in a mixture of THF (200 ml) and methanol (150 ml) was stirred under hydrogen atmosphere at room temperature for 4 hours. After removal of insoluble materials by filtration, the filtrate was concentrated to dryness. Recrystallization of the resultant crystalline residue from ethyl acetate-hexane afforded colorless crystals (18.7 g, 89%), m.p. 178-180 C. 1 H-NMR(200 MHz,DMSO-d6) delta: 2.15(3H,s), 6.30(2H,brs), 6.58(1H,d), 6.95(1H,dd), 6.97(1H,br), 7.34(1H,d), 7.64(1H,br) IR(KBr) cm-1: 3380, 3200, 1645, 1580, 1552
EXAMPLE 4 (6-Methyl-3,4-dihydro-quinazolin-2-yl)-(2-phenoxy-ethyl)-amine a) 2-Aminomethyl-4-methyl-phenylamine Under an atmosphere of argon, a solution <strong>[40545-33-3]2-amino-5-methylbenzamide</strong> (1.2 g, 80 mmol) in THF (25 ml) was added to a suspension of LiAlH4 (1.54 g, 40 mmol) in THF (25 ml) over 20 min. The suspension was heated to reflux (4 h). For workup, the mixture was cooled to 0 C., and 1.5 ml H2O, 3 ml 4n NaOH, and 3 ml H2O were added subsequently. The suspension was dried (Na2SO4), and evaporated under reduced pressure. The title compound (700 mg, 63%) was isolated from the residue by chromatographic purification (silica gel, CH2Cl2/MeOH (2M NH3)=9:1). MS: m/e=136 [M+]. 1H NMR (CDCl3): delta 2.23 (3H, s), 3.86 (2H, s), 6.61 (1H, d), 6.88 (2H, m).
N-[[[2-(Aminocarbonyl)-4-methylphenyl]amino]thioxomethyl]-4-methylbenzamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
EXAMPLE 14 N-[[[2-(Aminocarbonyl)-4-methylphenyl]amino]thioxomethyl]-4-methylbenzamide To a stirred mixture of 3 g of <strong>[40545-33-3]2-amino-5-methylbenzamide</strong> and 200 ml of ether was added dropwise, a solution of 3.7 g of 4-methylbenzoyl isothiocyanate in 100 ml of ether over 3 minutes. After 24 hours, the solid was collected, giving 6 g of the desired product as off-white crystals, mp 208-209 C. (dec.).
EXAMPLE 14 N-(1,4-Dihydro-6-methyl-4-oxo-2-quinazolinyl)-4-methylbenzamide To a stirred mixture of 3 g of <strong>[40545-33-3]2-amino-5-methylbenzamide</strong> and 200 ml of ether was added dropwise, a solution of 3.7 g of 4-methylbenzoyl isothiocyanate in 100 ml of ether over 30 minutes. After 24 hours the solid was collected, giving 6 g of N-[[[2-(aminocarbonyl)-4-methylphenyl]amino]thioxomethyl]-4-methylbenzamide.
With sodium hydroxide; In tetrahydrofuran; dichloromethane; water;
EXAMPLE 12 2-[[(Benzoylamino)thioxomethyl)amino]-5-methylbenzamide A mixture of 15 g of 2-amino-5-methylbenzoic acid, 16 g of 1,1-carbonyldiimidazole and 500 ml of tetrahydrofuran was stirred for 2 hours at room temperature and then saturated with anhydrous ammonia with ice bath cooling. After 24 hours, 50 ml of water was added and the mixture was concentrated under reduced pressure to a solid residue. This solid Was partially dissolved in 500 ml of dichloromethane and then washed with 200 ml of 0.1 N sodium hydroxide and 200 ml of water. The dichloromethane solution was dried and concentrated to a solid Which Was crystallized from ethyl acetate/hexane, giving 3.0 g of 2-amino-5-methylbenzamide as straw-colored crystals, mp 171-174 C.
2-[[(Benzoylamino)thioxomethyl)amino]-5-methylbenzamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
To a stirred mixture of 4.5 g of <strong>[40545-33-3]2-amino-5-methylbenzamide</strong> and 200 ml of ether was added dropwise, a solution of 4.9 g benzoyl isothiocyanate in 100 ml of ether over 20 minutes. After stirring overnight, the solid was collected, giving 8.7 g of the desired product as white crystals, mp 198-201 C. (dec.).
EXAMPLE 11 N-(1,4-Dihydro-6-methyl-4-oxo-2-quinazolinyl)benzamide To a stirred mixture of 4.5 g of <strong>[40545-33-3]2-amino-5-methylbenzamide</strong> and 200 ml of ether was added dropwise, a solution of 4.9 g of benzoyl isothiocyanate in 100 ml of ether over 20 minutes. After stirring overnight, the solid was collected, giving 8.7 g of 2-[[(benzoylamino)thioxomethyl]amino]-5-methylbenzamide.
2-(4-fluorophenyl)-6-methylquinazolin-4(3H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
83%
With iodine; potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 16h;
A mixture of 2~amino-5-methylbenzamide (1.0 g, 6.7 mmol), 4- fluorobenzaldehyde (0.83 g, 6.7 mmol), iodine (2.03 g, 8.0 mmol), and potassium carbonate (1.38 g, 10 mmol) in DMF (50 mL) was stirred at 8O0C for 16 hours. The reaction mixture was cooled to 2O0C and poured into icy water. The solid was collected by filtration, washed with water, and air dried to give 2-(4-fluoro-phenyl)- 6-methyl-3H-quinazolin-4-one (1.41 g, 83%). A solution of 2-(4-fluoro-phenyl)-6- methyl~3H-quinazolin-4-one (1.4 g, 5.5 mmol), NBS (0.98 g, 5.6 mmol), and benzoyl peroxide (67.0 mg, 0,276 mmol) in AcOH (150 mL) and chloroform (150 mL) was stirred at 8O0C for 5 hours with light shedding on. The reaction mixture was cooled to 2O0C and concentrated using a rotary evaporator to yield the crude bromide. A solution of the above crude bromide in DMF (20 mL) and 1 ,4-dioxane (100 mL) was mixed with morpholine (10 mL) and stirred at 8O0C for 4 hours. The reaction was quenched by adding water (200 mL), extracted with dichloromethane (3x100 mL), and concentrated using a rotary evaporator. The residue was further purified by column (SiO2, Hexanes/EtOAc/MeOH = 4:3:1) to yield 2-(4-fluoro- EPO <DP n="105"/>phenyl)-6-morpholin-4-ylmethyl-3H-quinazolin-4-one (0.89 g, 48% over two steps). A solution of 2-(4-fluoro-phenyl)-6-morpholin-4-ylmethyl-3H-quinazolin-4-one (0.89 g, 2.62 mmol) in dichloromethane (100 mL) and MeOH (50 mL) was mixed with HCI in ether (8 mL, 16 mmol) and stirred for 1 hour. The reaction was concentrated using a rotary evaporator. The solid was rinsed with DCM (50 mL) and MeOH (5 mL), collected by filtration, washed with DCM-MeOH (10:1 ) to afford 2-(4-fluorophenyl)-6-(morpholinomethyl)quinazolin-4(3H)-one (0.82 g, 76%) as an off-white solid; MS (ES) m/z: 340 (M+1); MP 321.8-323.30C
With triethylamine; In tetrahydrofuran; at 0 - 20℃; for 3h;
Step 3 To a solution of <strong>[40545-33-3]2-amino-5-methylbenzamide</strong> (5.80 g, 38.6 mmol) and triethylamine (4.69 g, 46.3 mmol) in THF (200 mL) was added dropwise ethyl chloroglyoxylate (5.80 g, 42.5 mmol) under ice-cooling, and the mixture was stirred at room temperature for 3 hr. The reaction mixture was diluted with ethyl acetate, washed with water and saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue was washed with ethanol to give ethyl ((2-(aminocarbonyl)-4-methylphenyl)amino)(oxo)acetate as a white powder (9.83 g, 100%).
100%
With triethylamine; In tetrahydrofuran; at 35℃; for 3h;Cooling with ice;
Step 3 To a solution of <strong>[40545-33-3]2-amino-5-methylbenzamide</strong> (5.80 g, 38.6 mmol) and triethylamine (4.69 g, 46.3 mmol) in THF (200 mL) was added dropwise ethyl chloroglyoxylate (5.80 g, 42.5 mmol) under ice-cooling, and the mixture was stirred at room temperature for 3 hrs. The reaction mixture was diluted with ethyl acetate, washed with water and saturated brine, dried over sodium sulfate and concentrated under reduced pressure. The obtained concentrated residue was washed with ethanol to give ethyl ((2-(aminocarbonyl)-4-methylphenyl)amino)(oxo)acetate as a white powder (9.83 g, 100%).
General procedure: To a cold (0-5 C) stirred suspension of aminobenzamides 10a-c (0.016 mol) in pyridine (13 ml), 0.016 mol of the appropriate 3-phenylacryloyl chloride 11c-k was added over 30 min. After addition was complete, the solution was stirred for 24 h and then poured onto crushed ice. The precipitate was removed by filtration, washed with water, and crystallized from ethanol.
With potassium hydroxide; In toluene; at 90℃; for 20h;
General procedure: To an oven-dried 20 cm3 test tube with a ground-in stopperequipped with a stir bar were added anthranilamide (1.0 mmol), benzyl alcohol (1.0 mmol), KOH (2.0 mmol),and 4 cm3 toluene. The test tube was put in an oil bath potpreheated at 90 C and the mixture was stirred for 20 h at90 C. After cooling to room temperature, the reactionmixture was added about 5 g silica gel and directly condensedon a rotator under vacuum. The resulting residualwas transferred to a silica gel chromatography column andeluted with a solution of petroleum ether and ethyl acetate[4/1 (v/v)] to give a white solid 2-phenyl-4(3H)-quinazolinone.For some products (3f, 3g, 3n, and 3t) onlysparingly soluble in ethyl acetate, the reaction mixtureswere condensed in vacuo on a rotary evaporator. Theresiduals were washed three times with water and oncewith ethyl acetate, and then dried in an infrared oven togive the desired products pure enough for NMR analysis.
95.4%
In synthesizing the right amount of solvent to in DMF, by adding 100mmol formula (I) compounds and 150mmol formula (II) compound, stirring and mixing 12 minutes, then adding 10mmol four b nitrile four fluoboric acid palladium, 50mmol trifluro sulfonic acid scandium and 12mmol 1 - benzyl -3 - methyl imidazole double (trifluoromethane sulfonyl) iminium salts, then heating to 65 C reaction 9 hours; After the reaction, the reaction system natural cooling to room temperature, filtered, deionized water is added to the filtrate, then adding sodium bicarbonate in and to the system for pH 6.5 - 7.5, then dichloromethane is used for extraction three times, the combined organic phase, vacuum concentration, the resulting ethanol can be recovered and re-crystallization, filtering solid, vacuum drying, to obtain the compound of formula (III), and the yield is 95.4%.
2-phenyl-6-methyl-2,3-dihydroquinazolin-4(1H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In water; for 2h;Reflux;
A mixture of <strong>[40545-33-3]2-amino-5-methylbenzamide</strong> (150 mg, 1 mmol)), Benzaldehyde (106 mg, lmmol), Water (1 · OmL)And then added to 5mL single-mouth bottle. The mixture was reacted at reflux temperature for 2 hours and then cooled to room temperature. Then join[Cp * Ir (H20) 3] [0Tf] 2 (6.8 mg, 0. ol mmol, 1 mol%) was reacted at reflux temperature for 1 hour and then cooled to room temperatureTheThe solvent was removed under vacuum under reduced pressure and then passed through a column chromatography (developing solvent): Ethyl acetate / n-hexane) to give the pure title compoundObjects,Yield: 81%.
General procedure: A dry 50 mL flask was charged with 2-aminobenzamide 1 (1.1 mmol), 5,5-dimethyl-1,3-cyclohexanedione 2 (1.0 mmol), iodine (0.026 g, 0.01 mmol) and toluene (10.0 mL). The mixture was stirred at 80 C until the reactant 1 was consumed. Then, another equivalent of 2-aminobenzamide was added to the mixture, and refluxed for a few hours. After the completion of the reaction monitored by TLC, toluene was recovered by distillation under reduced pressure, and the residue was purified by silica column chromatography using ethyl acetate and petroleum ether (1:2) as the eluent to give products 6.
General procedure: A dry 50 mL flask was charged with 2-aminobenzamides 1 (2.1 mmol), 5,5-dimethyl-1,3-cyclohexanedione 2 (0.280 g, 2.0 mmol), iodine (0.026 g, 0.01 mmol) and toluene (10.0 mL). The mixture was stirred at 50 C until the reactant 1 was consumed. After the completion of the reaction monitored by TLC, toluene was recovered by distillation under reduced pressure, and the residue was purified by recrystallization in EtOH to give products 4.
General procedure: A dry 50 mL flask was charged with 2-aminobenzamides 1 (1.1 mmol), 5,5-dimethyl-1,3-cyclohexanedione 2 (0.280 g, 1.0 mmol), iodine (0.026 g, 0.01 mmol) and toluene (10.0 mL). The mixture was stirred at 80 C until the reactant 1 was consumed. After the completion of the reaction monitored by TLC, toluene was recovered by distillation under reduced pressure, and the residue was purified by silica column chromatography using ethyl acetate and petroleum ether (1:3) as the eluent to give products 5.
General procedure: A dry 50 mL flask was charged with 2-aminobenzamides 1 (2.1 mmol), 5,5-dimethyl-1,3-cyclohexanedione 2 (1.0 mmol), iodine (0.026 g, 0.01 mmol) and toluene (10.0 mL). The mixture was stirred at reflux until the reactant 1 was consumed. After the completion of the reaction monitored by TLC, toluene was recovered by distillation under reduced pressure, and the residue was purified by silica column chromatography using ethyl acetate and petroleum ether (1:3) as the eluent to give products 3.
General procedure: A dry 50 mL flask was charged with 2-aminobenzamides 1 (2.1 mmol), 5,5-dimethyl-1,3-cyclohexanedione 2 (1.0 mmol), iodine (0.026 g, 0.01 mmol) and toluene (10.0 mL). The mixture was stirred at reflux until the reactant 1 was consumed. After the completion of the reaction monitored by TLC, toluene was recovered by distillation under reduced pressure, and the residue was purified by silica column chromatography using ethyl acetate and petroleum ether (1:3) as the eluent to give products 3.
General procedure: A dry 50 mL flask was charged with 2-aminobenzamides 1 (2.1 mmol), 5,5-dimethyl-1,3-cyclohexanedione 2 (1.0 mmol), iodine (0.026 g, 0.01 mmol) and toluene (10.0 mL). The mixture was stirred at reflux until the reactant 1 was consumed. After the completion of the reaction monitored by TLC, toluene was recovered by distillation under reduced pressure, and the residue was purified by silica column chromatography using ethyl acetate and petroleum ether (1:3) as the eluent to give products 3.
General procedure: To a cold (0-5 C) stirred suspension of aminobenzamides 2a-g (0.016 mol) in pyridine (13 ml), 0.016 mol of the appropriate cinnamoyl chloride 3a-e, 3-phenylpropioloyl chloride 3f-k and 3-phenylpropanoyl chloride 3l-o was added over 30 min. After addition was complete, the solution was stirred for 24 h and then poured onto crushed ice. The precipitate was removed by filtration, washed with water, and crystallized from the appropriate solvent.
General procedure: To a cold (0-5 C) stirred suspension of aminobenzamides 2a-g (0.016 mol) in pyridine (13 ml), 0.016 mol of the appropriate cinnamoyl chloride 3a-e, 3-phenylpropioloyl chloride 3f-k and 3-phenylpropanoyl chloride 3l-o was added over 30 min. After addition was complete, the solution was stirred for 24 h and then poured onto crushed ice. The precipitate was removed by filtration, washed with water, and crystallized from the appropriate solvent.
General procedure: To a cold (0-5 C) stirred suspension of aminobenzamides 2a-g (0.016 mol) in pyridine (13 ml), 0.016 mol of the appropriate cinnamoyl chloride 3a-e, 3-phenylpropioloyl chloride 3f-k and 3-phenylpropanoyl chloride 3l-o was added over 30 min. After addition was complete, the solution was stirred for 24 h and then poured onto crushed ice. The precipitate was removed by filtration, washed with water, and crystallized from the appropriate solvent.
2-(4-pentynyl)-6-methyl-4(3H)-quinazolinone[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
General procedure: To a solution of 5-hexynoic acid (3.0 mmol) in dryCH2Cl2 (5 mL) was added EDCI (3.1 mmol) and HOBt(3.1 mmol). The resulting mixture was stirred at rt for 2 h. Then substituted or unsubstituted 2-aminobenzamide (3.0 mmol) wasadded, and the reaction mixture was stirred at rt for 12 h whilebeing monitored by TLC. After the addition of H2O (10 mL) themixture was extracted with ethyl acetate (3 × 20 mL). Theorganic layers were combined and concentrated under vacuumto give the amide intermediate.
2-(3-butynyl)-6-methyl-4(3H)-quinazolinone[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
General procedure: To a solution of 5-hexynoic acid (3.0 mmol) in dryCH2Cl2 (5 mL) was added EDCI (3.1 mmol) and HOBt(3.1 mmol). The resulting mixture was stirred at rt for 2 h. Then substituted or unsubstituted 2-aminobenzamide (3.0 mmol) wasadded, and the reaction mixture was stirred at rt for 12 h whilebeing monitored by TLC. After the addition of H2O (10 mL) themixture was extracted with ethyl acetate (3 × 20 mL). Theorganic layers were combined and concentrated under vacuumto give the amide intermediate.
6-methyl-2-(3-(trifluoromethoxy)phenyl)quinazolin-4(3H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
95%
With sodium hydrogensulfite; In N,N-dimethyl acetamide; at 150℃;
General procedure: Sodium hydrogen sulfite (4 mmol) was added to a solution of anthranilamide 1 (2 mmol) and benzaldehyde 2 (2 mmol) in N,N- dimethylacetamide (5 mL). The mixture was heated under continuous stirring at 150 o C for 2-3 h and poured into ice water. The precipitate was then filtered, washed with water followed byethanol, and dried to yield the 2-arylquinazolinones 3-31.
6-methyl-2-(2-(trifluoromethoxy)phenyl)quinazolin-4(3H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
78%
With sodium hydrogensulfite; In N,N-dimethyl acetamide; at 150℃;
General procedure: Sodium hydrogen sulfite (4 mmol) was added to a solution of anthranilamide 1 (2 mmol) and benzaldehyde 2 (2 mmol) in N,N- dimethylacetamide (5 mL). The mixture was heated under continuous stirring at 150 o C for 2-3 h and poured into ice water. The precipitate was then filtered, washed with water followed byethanol, and dried to yield the 2-arylquinazolinones 3-31.
With [Cp*Ir(2,2'-bpyO)(H2O)]; caesium carbonate; at 130℃; for 2h;Inert atmosphere; Microwave irradiation;
2-amino-5-methylbenzamide (75 mg, 0.5 mmol), [Cp * Ir (2,2'-bpyO) (H2O)](5.4 mg, 0.005 mmol, 1 mol%),Cesium carbonate (49 mg, 0.15 mmol, 0.3 equiv.) And methanol (0.5 ml) were sequentially added to a dried 5 mL microwave reaction tube.Microwave tube nitrogen protection,Placed in a single mode pressure microwave synthesizer (Discover CEM,USA). After the reaction mixture was reacted at 130 C for 2 hours,Cool to room temperature. Rotary evaporation to remove the solvent,Then, column chromatography (developing solvent: petroleum ether / ethyl acetate)The pure target compound was obtained in a yield of 90%
With water; potassium carbonate; In water; at 150℃; for 0.5h;Microwave irradiation;
General procedure: Adapted from a literature procedure,1 the appropriate organonitrile (1.0 eq.) and K2CO3(0.2eq.)wereaddedtoamicrowavetubewithastir-barwithdeionizedwater(8.5mLpermmolsubstrate).Afterirradiationundermicrowaveat150Cfor30minutes,thereactionmixturewascooled,extractedwithEtOAc(320mL),thecombinedphasesdriedoverMgSO4andexcesssolventremovedinvacuo.TheresiduewaspurifiedbyFCC,ifrequired,togivethetitlecompound.
90%
With water extract of pomelo, peel; at 150℃; for 0.5h;Sealed tube; Green chemistry;
General procedure: Benzonitrile 1a (103 mg, 1.0 mmol) and WEPPA (2.0 mL) were added into a 10-mL closed tubewith a stir bar. Then the reaction was stirred in a closed vessel synthesis reactor at 150 C for 0.5 h.After cooling to ambient temperature, the resulting precipitate was collected by filtration, washed withice water, and further dried in a vacuum drying oven. The filtrate was evaporated under reducedpressure. The resultant residue was purified by silica gel column chromatography (eluent: petroleumether (35-60 C)/EtOAc = 2:1 to 0:1, v/v). Finally, these two parts were combined to produce the desiredbenzamide 2a with a 94% yield.
General procedure: To a solution of 2-amino-5-methylbenzamide (1.5 g,10 mmol) in THF (20 mL) was added triphosgene (0.99 g, 3.3 mmol) portionwise about 20 min. The mixture was cooled to rt when the reaction was completed. Through filtration, the crude isatoic anhydride was got. A stirred solution of isatoic anhydride was suspending in THF which was heated to 60C, then the solution of amine was added dropwise. Progress of the reaction was monitored using TLC. After completion of the reaction, the resulting solution was cooled to room temperature and the solvent was removed under high vacuum to give the crude product. Then recrystallization from Et2O afforded the pure product.
9-fluoro-2-methylindolo[2,1-b]quinazoline-6,12-dione[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
44%
In a 25 mL round bottom flask, 1 d (130.2 mg, 0.6 mmol), bisMethylsulfoxide (3 mL) and iodine (152 mg, 0.6 mmol) were added and the mixture was heated and stirred at 110 C. for 3 h, then cooled to room temperature, added2b (60.1 mg, 0.4 mmol), CuBr (11.5 mg, 0.08 mmol) and K2CO3 (221 mg, 1.6 mmol) were added and stirred at room temperatureShould be 5h, then heated to 100 heated reaction 3h. After completion of the reaction, saturated ammonium chloride solution was added to the reaction vessel to quenchThe reaction was extracted with methylene chloride. The combined organic phases were washed with deionized water and saturated sodium chloride solution and dried over anhydrous sodium sulfate. TooFiltration and spin-drying gave 9-fluoro-2-methylindolo [2,1-b] quinazolin-6,12-dione 3h (49 mg, 44%).
9-chloro-2-methylindolo[2,1-b]quinazoline-6,12-dione[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
61%
In the manner described in Example 1, 1e (140.1 mg, 0.6 mmol), bisMethylsulfoxide (3 mL) and iodine (152 mg, 0.6 mmol) were added and the mixture was heated and stirred at 110 C. for 3 h, then cooled to room temperature, added2b (60.1 mg, 0.4 mmol), CuBr (11.5 mg, 0.08 mmol) and K2CO3 (221 mg, 1.6 mmol) were added and stirred at room temperatureShould be 5h, then heated to 100 heated reaction 3h. After completion of the reaction, saturated ammonium chloride solution was added to the reaction vessel to quenchThe reaction was extracted with methylene chloride. The combined organic phases were washed with deionized water and saturated sodium chloride solution and dried over anhydrous sodium sulfate. TooThe product was isolated by filtration on a silica gel column (petroleum ether / ethyl acetate = 3/1, v / v)6,12-dione 3i (72 mg, 61%).
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
