* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Reference：
[1] Journal of the Chemical Society, 1956, p. 1045,1053
2
[ 21038-66-4 ]
[ 126728-20-9 ]
Yield
Reaction Conditions
Operation in experiment
84.9%
at 105℃; for 24 h;
To a 500 mL two-neck round bottom flask equipped with a thermometer and a reflux condenser, Intermediate 12 (10.0g, 0.061 mol) and phosphorous oxychloride (200 mL) were added, mixed uniformly, heated to reflux at 105 °C and stirred for 24 hours. Thereafter, the reaction product was subjected to vacuum distillation for removal of phosphorus oxychloride. The remaining syrupy substance was poured onto 200 g of crushed ice, and immediately extracted 3 times with chloroform, 150 mL each time. The extracts were combined, washed 3 times with saturated brine, concentrated, and separated through a silica gel column (eluent: petroleum ether/ethyl acetate), to give 10.36 g of a white solid product, yield 84.9percent. [0085] 1H-NMR (400 MHz, CDCl3) δ ppm: 9.34 (1H, m), 8.66 (1H, m), 7.76 (1H, m); EI-MS (m/z): 199.0[M]+
84.9%
at 105℃; for 24 h;
To a 500 mL two-neck round bottom flask equipped with a thermometer and a reflux condenser, Intermediate 12 (10.0 g, 0.061 mol) and phosphorous oxychloride (200 mL) were added, mixed uniformly, heated to reflux at 105° C. and stirred for 24 hours. Thereafter, the reaction product was subjected to vacuum distillation for removal of phosphorus oxychloride. The remaining syrupy substance was poured onto 200 g of crushed ice, and immediately extracted 3 times with chloroform, 150 mL each time. The extracts were combined, washed 3 times with saturated brine, concentrated, and separated through a silica gel column (eluent: petroleum ether/ethyl acetate), to give 10.36 g of a white solid product, yield 84.9percent.1H-NMR (400 MHz, CDCl3) δ ppm: 9.34 (1H, m), 8.66 (1H, m), 7.76 (1H, m); EI-MS (m/z): 199.0[M]+.
Reference：
[1] Molecules, 2012, vol. 17, # 8, p. 9961 - 9970
[2] Patent: EP2805947, 2014, A1, . Location in patent: Paragraph 0084-0085
[3] Patent: US2015/126500, 2015, A1, . Location in patent: Paragraph 0137; 0138
[4] Journal of Organic Chemistry, 2011, vol. 76, # 10, p. 4149 - 4153
[5] Tetrahedron Letters, 2005, vol. 46, # 35, p. 5851 - 5855
[6] Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 6, p. 2031 - 2044
[7] Archiv der Pharmazie, 2006, vol. 339, # 4, p. 182 - 192
[8] Patent: US2007/281949, 2007, A1, . Location in patent: Page/Page column 100
[9] European Journal of Medicinal Chemistry, 2012, vol. 47, # 1, p. 283 - 298
[10] Journal of Medicinal Chemistry, 2014, vol. 57, # 1, p. 144 - 158
3
[ 21038-66-4 ]
[ 126728-20-9 ]
Yield
Reaction Conditions
Operation in experiment
54%
at 135℃;
(2) 1 g of intermediate B was added4With POCl3, PCl5The reaction was refluxed at 135 ° C to give the intermediate C4, Yield 54percent; reaction equation is as follows:
Reference：
[1] Patent: CN106083742, 2016, A, . Location in patent: Paragraph 0211; 0214; 0215
[2] Patent: WO2005/49033, 2005, A1, . Location in patent: Page/Page column 110
[3] Journal of the Chemical Society, 1956, p. 1045,1053
[4] Journal of the Chemical Society, 1949, p. 2582,2584
[5] Journal of the American Chemical Society, 1955, vol. 77, p. 2256,2259
[6] Patent: US2006/199804, 2006, A1, . Location in patent: Page/Page column 40
[7] Patent: WO2011/104183, 2011, A1, . Location in patent: Page/Page column 45
[8] European Journal of Medicinal Chemistry, 2011, vol. 46, # 9, p. 3887 - 3899
[9] Patent: US2012/316184, 2012, A1, . Location in patent: Page/Page column 21
[10] Arkivoc, 2014, vol. 2014, # 2, p. 187 - 206
[11] ChemMedChem, 2014, vol. 9, # 11, p. 2516 - 2527
[12] RSC Advances, 2017, vol. 7, # 82, p. 52227 - 52237
[13] Patent: US2006/199803, 2006, A1, . Location in patent: Page/Page column 13
A finely powdered mixture of 2-aminonicotinic acid (7.0 g, 50.7 mmol) and urea (13.0 g, 216 mmol) was heated to180-190 C and maintained for 15 minutes at the same temperature. The temperature was gradually raised to200 C and the clear melt started to solidify. The temperature was raised to210 C and the heating was discontinued. The mixture was cooled to room temperature and 2 NNaOH solution (70 ml) was added. It was heated at50-55 C to get a clear solution. This warm solution was saturated with carbon dioxide, cooled and filtered and the solid was washed with water (2 x 25ml) to give desired product (7. 71 g,76%). H NMR 8 7.16 (m, 1 H), 8.22 (d, J = 6.4 Hz, 1 H), 8. 53 (m, 1 H).
26%
at 200℃; for 5h;
(1) 4 g of 2-aminonicotinic acid (starting material A4), 20 g of urea was refluxed at 200 C for 5 h to give intermediate B1, The yield of 26%; reaction equation is as follows:
A mixture of 2-aminopicotinic acid (1.4 g, 10 mmol) and urea (3.7 g, 61 mmol) was heated to 190C for 3 hours, after which it was cooled to 100C, and water, then aqueous hydrochloric acid (1 M) were added, until an acidic pH was reached. The mixture was refluxed for an hour before being cooled to ambient temperature. The resulting solid was filtered and dried in vacuo. 1H NMR (DMSO-d6): 7.24 (dd, 1 H), 8.26 (dd, 1 H), 8.59 (dd, 1 H), 10.95 (s, 1 H), 1 1.70 (s, 1 H).
In neat (no solvent); at 150℃; for 12h;
General procedure: The typical procedure to aromatic fused pyrimidine-2,4(1H,3H)-diones (2) is as follows. Aromatic-3-amine-2-carboxylic acid (0.1 mol) and urea (2 mol) were both mixed in a flask and then heated at 150 C for 12 h. When the mixture was cooled down to 100 C, 40 mL of water was added and the resultant mixture was stirred for another 10 min to dissolve the unreacted urea. After the reaction mixture was cooled down to room temperature, it was filtered and 400 mL, 1 mol/L NaOH aqueous solution was then added. Another 1 h later 55 mL of acetic acid was dropwise added for acidification and the resultant light yellow or white precipitates were filtered and dried to give the desired product 2 in a yield of 80-95%.
f) Preparation of 1H-pyrido[2,3-d]pyrimidine-2,4-dione: A mixture of 2-aminopicotinic acid (1.4 g, 10 mmol) and urea (3.7 g, 61 mmol) was heated to 190 C. for 3 hours, after which it was cooled to 100 C., and water, then aqueous hydrochloric acid (1 M) were added, until an acidic pH was reached. The mixture was refluxed for an hour before being cooled to ambient temperature. The resulting solid was filtered and dried in vacuo. 1H NMR (DMSO-d6): 7.24 (dd, 1H), 8.26 (dd, 1H), 8.59 (dd, 1H), 10.95 (s, 1H), 11.70 (s, 1H).
With lead(IV) acetate In <i>N</i>-methyl-acetamide
VIII Preparation of Pyrido[2,3-d]Pyrimidine 2,4(1H,3H)-Dione
EXAMPLE VIII Preparation of Pyrido[2,3-d]Pyrimidine 2,4(1H,3H)-Dione A 50 ml. flask was charged with 0.9 g. pyridine-2,3-dicarboxamide suspended in 10 ml. dimethylformamide. A 2.4 g. portion of lead tetra-acetate was added to the suspension, and the reaction mixture was stirred at 50°-60° for 20 minutes and filtered. Sublimation of the residue at 200° at an absolute pressure of 0.01 mm. Hg gave a yield of 0.8 g. pyrido[2,3-d]pyrimidine-2,4 (1H,3H)-dione, melting point 360°, and represented 90 percent of theory based on the pyridine-2,3-dicarboxamide. The structure was confirmed by infrared spectroscopy.
With phosphorus pentachloride; trichlorophosphate; at 135℃;
(2) 1 g of intermediate B was added4With POCl3, PCl5The reaction was refluxed at 135 C to give the intermediate C4, Yield 54%; reaction equation is as follows:
With N-ethyl-N,N-diisopropylamine; trichlorophosphate; In toluene; at 100℃; for 3h;
To a solution of 1H-Pyrido[2,3-d]pyrimidine-2,4-dione (5.0 g, 30.65 mmol) in toluene (50 ml), under an inert atmosphere, was added N,N-diiospropylethylamine (19.81 g, 153.2 mmol). Phosporous oxychloride (23.50 g, 153.2 mmol) was then added to the mixture dropwise before the reaction was heated to 100 C. for 3 hours. The mixture was then concentrated in vacuo and then diluted in CH2Cl2 (200 ml) before being poured carefully into ice water (300 ml). The biphasic mixture was then filtered through a thin pad of Celite, neutralized and separated. The aqueous phase was extracted further with CH2Cl2 (2×100 ml) and the combined organic extract dried (sodium sulfate), filtered and concentrated in vacuo to give a thick syrup which was used in it crude form for the next step.
With N,N-diethylaniline; trichlorophosphate; for 3h;Reflux;
A mixture of 1 H-pyrido[2,3-d]pyrimidine-2,4-dione (1.4 g, 8.5 mmol) and Lambda/,/V-diethylaniline (1 .4 ml_, 8.5 mmol) in phosphorus oxychloride (8 ml) was refluxed for 3 hours. It was then concentrated in vacuo and the residue was carefully poured on an ice-cold saturated aqueous solution of sodium bicarbonate. The suspension was diluted with ethyl acetate and the organic layer was decanted, dried over magnesium sulphate and concentrated in vacuo. The crude oil was purified by flash chromatography on silica gel (eluent gradient: 0% to 60% ethyl acetate in cyclohexane). The title compound was obtained as a white solid. 1H NMR (CDCI3): 7.72 (dd, 1 H), 8.64 (dd, 1 H), 9.43 (dd, 1 H).
With N,N-dimethyl-formamide; trichlorophosphate; for 48h;Reflux;
General procedure: A mixture of commercially available 2,4-(1H,3H)-quinazolinedione (6.0 mmol), POCl3 (5 mL) and N,N-DMF (catalytic amount) was stirred and heated under reflux for 48 h. The solvents were removed under vacuum and cold water (0 C, 25 mL) and chloroform (25 mL) were added. The organic layer was washed with water (3 × 20 mL) and dried over anhydrous sodium sulfate. The solvent was removed under vacuum and the product was used immediately without further purification.
With N,N-diethylaniline; trichlorophosphate; for 3h;Reflux;
g) Preparation of 2,4-dichloro-pyrido[2,3-d]pyrimidine: A mixture of 1H-pyrido[2,3-d]pyrimidine-2,4-dione (1.4 g, 8.5 mmol) and N,N-diethylaniline (1.4 mL, 8.5 mmol) in phosphorus oxychloride (8 ml) was refluxed for 3 hours. It was then concentrated in vacuo and the residue was carefully poured on an ice-cold saturated aqueous solution of sodium bicarbonate. The suspension was diluted with ethyl acetate and the organic layer was decanted, dried over magnesium sulphate and concentrated in vacuo. The crude oil was purified by flash chromatography on silica gel (eluent gradient: 0% to 60% ethyl acetate in cyclohexane). The title compound was obtained as a white solid. 1H NMR (CDCl3): 7.72 (dd, 1H), 8.64 (dd, 1H), 9.43 (dd, 1H).
With diisopropylamine; trichlorophosphate; at 20℃; for 5h;
(ii) 2,4-Dichloro-pyridopyrimidines (3) The appropriate 1H-pyridopyrimidine-2,4-dione (2)(1 equivalent) was dissolved in POCl3 (44 equivalents). To this mixture was added N,N-diisopropylamine (2.8 equivalents) in a dropwise fashion. The reaction was stirred at room temperature under an inert atmosphere for 5 hours. After this time the mixture was concentrated in vacuo while taking care to keep the temperature below 30 C. The resulting black residue was poured onto crushed ice. The mixture was extracted with CH2Cl2 (×2) and the organic extracts then washed with water, dried (MgSO4), filtered and concentrated in vacuo to provide a tar like material that corresponded to the desired product in suitably clean form to be used without any further purification. 3a: 2,4-Dichloro-pyrido[2,3-d]pyrimidine: m/z (LC-MS, ESP): 200 [M+H]+R/T=3.60 mins 3b: 2,4-Dichloro-pyrido[3,4-d]pyrimidine: m/z (LC-MS, ESP): 200 [M+H]+, R/T=3.82 mins 3c: 2,4-Dichloro-pyrido[3,2-d]pyrimidine: m/z (LC-MS, ESP): 200 [M+H]+,R/T=3.80 mins.
To a 500 mL two-neck round bottom flask equipped with a thermometer and a reflux condenser, Intermediate 12 (10.0g, 0.061 mol) and phosphorous oxychloride (200 mL) were added, mixed uniformly, heated to reflux at 105 C and stirred for 24 hours. Thereafter, the reaction product was subjected to vacuum distillation for removal of phosphorus oxychloride. The remaining syrupy substance was poured onto 200 g of crushed ice, and immediately extracted 3 times with chloroform, 150 mL each time. The extracts were combined, washed 3 times with saturated brine, concentrated, and separated through a silica gel column (eluent: petroleum ether/ethyl acetate), to give 10.36 g of a white solid product, yield 84.9%. [0085] 1H-NMR (400 MHz, CDCl3) delta ppm: 9.34 (1H, m), 8.66 (1H, m), 7.76 (1H, m); EI-MS (m/z): 199.0[M]+
84.9%
With trichlorophosphate; at 105℃; for 24h;
To a 500 mL two-neck round bottom flask equipped with a thermometer and a reflux condenser, Intermediate 12 (10.0 g, 0.061 mol) and phosphorous oxychloride (200 mL) were added, mixed uniformly, heated to reflux at 105 C. and stirred for 24 hours. Thereafter, the reaction product was subjected to vacuum distillation for removal of phosphorus oxychloride. The remaining syrupy substance was poured onto 200 g of crushed ice, and immediately extracted 3 times with chloroform, 150 mL each time. The extracts were combined, washed 3 times with saturated brine, concentrated, and separated through a silica gel column (eluent: petroleum ether/ethyl acetate), to give 10.36 g of a white solid product, yield 84.9%.1H-NMR (400 MHz, CDCl3) delta ppm: 9.34 (1H, m), 8.66 (1H, m), 7.76 (1H, m); EI-MS (m/z): 199.0[M]+.
With N,N-dimethyl-aniline; trichlorophosphate; for 5.5h;Heating / reflux;
Compound 356; 2,4-Dichloro-pyrido[2,3-d]pyrimidine; To a 100 mL flask was added Compound 355 (500 mg, 3.06 mmol), N,N-diethylaniline (1 mL), and POCl3 (10 mL). The reaction mixture was heated to reflux for 5.5 h. After cooled to room temp, the reaction was concentrated in vacuo. The residue was quenched with ice-water (50 mL) and was immediately extracted with CHCl3 (50 mL×3). The combined organic extracts was washed with water (50 mL), dried (MgSO4), filtered and concentrated to give crude the title Compound 356. The material was used for next step without purification.
With water; ammonium chloride; at 80 - 200℃; for 2.5h;
A slurry of 2-aminonicotinic acid (10 g, 72.5 mmol), ammonium chloride (39 g, 725 mmol) and potassium cyanate (30 g, 362 mmol) in water (80 ml) was heated to 80 C. and maintained at this temperature with stirring for 30 minutes before being heated to 200 C. The mixture was stirred for 2 hours at this elevated temperature and then left to cool. Water (200 ml) was then added and the resultant mixture filtered. The solid was washed with hot water (100 ml) and then with cold water (2*100 ml) to give a yellow solid which corresponded to the title compound (11.79 g, 99%) in suitably clean form to be used without any further purification. m/z (LC-MSW, ESP):164 [M+H]+, R/T=2.11 mins.
With ammonium chloride; In water; at 20 - 200℃; for 2.66667h;
(i) 1H-Pyridopyrimidine-2, 4-diones (2) The appropriate amino acid (1)(1 equivalent), potassium cyanate (5 equivalents) and ammonium chloride (10 equivalents) were suspended in water. The slurry was heated (160 C.) and mixed manually for 2 hours as water vapour was expelled from the reaction vessel. The reaction temperature was then raised to 200 C. for 40 minutes before being cooled to 90 C. whereupon hot water was added and then the mixture was allowed to cool to room temperature. The precipitate that formed during cooling was removed by filtration, washed with water (twice), and diethyl ether (once) before being dried in a desiccator to give the desired product in suitably clean form to be used without further purification. 2a: 1H-Pyrido[2,3-d]pyrimidine-2,4-dione: m/z (LC-MS, ESP): does not ionise R/T=0.76 mins 2b: 1H-Pyrido[3,4-d]pyrimidine-2,4-dione: m/z (LC-MS, ESP): 164 [M-K+H]+, R/T=0.38 mins 2c: 1H-Pyrido[3,2-d]pyrimidine-2,4-dione: m/z (LC-MS, ESP): 164 [M-K+H]+,R/T=0.45 mins.
Stage #1: 1H-Pyrido[2,3-d]pyrimidine-2,4-dione With trichlorophosphate at 110℃; for 16h; Inert atmosphere;
Stage #2: With sodium hydroxide In water at 20℃; for 2h;
Stage #1: 1H-Pyrido[2,3-d]pyrimidine-2,4-dione With lithium hydroxide In dimethyl sulfoxide at 40℃; for 2h;
Stage #2: bromoacetic acid In dimethyl sulfoxide at 40℃; for 12h;
Stage #3: With hydrogenchloride In water regioselective reaction;
4.3.2 Synthesis of the aromatic fused pyrimidine-2,4(3H)-dione-1-yl acetic acid
General procedure: The typical procedure is as follows: 2 (10 mmol) and LiOH (25 mmol) was dissolved into DMSO (60 mL) and stirred at 40 °C for 2 h, to which a 5 mL DMSO solution of BrCH2COOH (10 mmol) was dropwise added inside within 5 min. The reaction was continued at 40 °C for 12 h. Then it was poured into 500 mL ethyl acetate. The resultant white or light yellow precipitates were collected and re-dissolved into 100 mL water. The water solution was adjusted to pH=6 using 4 M hydrochloric acid and then was put at 3-6 °C for 2 h. The precipitates (2) were then filtered out and the solution was again adjusted to pH=2 and put at 3-6 °C for another 2 h. The product 3 was filtered out in a typical yield shown in Tables 1 and 2, respectively. The yield for each compound of 3a-g was listed in Table 2.
With phosphorus pentachloride; trichlorophosphate at 160℃; for 2h; Microwave irradiation;
1 2,4,7-Trichloropyrido[3,2-d]pyrimidine (2)
In a 20 mL vial, 1.0 g (6.13 mmol, 1 equiv.) of 1H,3H-pyrido[3,2-c]pyrimidine-2,4-dione 1 is in suspension in 10 mL of phosphorus oxychloride and 7.65 g (36.7 mmol, 6.0 equiv.) of phosphorus pentachloride (PClS). The whole is heated with microwave irradiations to 160° C. After 2 hours of reaction, the POCl3 excess is evaporated under reduced pressure. The obtained residue is brought to 0° C. by means of an ice bath and solubilized in dichloromethane, the mixture is poured in a water/ice mixture without any basification. After returning to room temperature, the aqueous phase is extracted with dichloromethane. The organic phase is then dried on MgSO4, filtered, and then concentrated under reduced pressure. The thereby obtained residue is chromatographed on silica gel (petroleum ether/CH2Cl2, 40/60) in order to obtain white solid with a yield of 62%. MP: 165-166° C.; IR (ATR, Diamond, cm-1) ν: 3048, 2167, 1579, 1531, 1430, 1324, 1253, 1136, 1001, 872; 1H NMR (400 MHz, CDCl3) δ: 8.31 (d, 1H, J=2.2 Hz, H8), 9.03 (d, 1H, J=2.2 Hz, H6); 13C NMR (100 MHz, CDCl3) δ: 134.2 (CH), 135.1 (Cq), 138.5 (Cq), 148.8 (Cq), 152.7 (CH), 157.0 (Cq), 166.0 (Cq); HRMS (EI-MS): C7H235Cl3N3, calculated m/z 232.9314. found m/z 232.9323.
2-((1-benzyl-1H-pyrazol-4-yl)oxy)pyrido[2,3-d]pyrimidin-4(3H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
Multi-step reaction with 2 steps
1.1: trichlorophosphate / 16 h / 110 °C / Inert atmosphere
1.2: 2 h / 20 °C
2.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.08 h
2.2: 48 h / 110 °C / Inert atmosphere
With 1,5-diazabicyclo[4.3.0]non-5-ene 2,2,2-trifluoroethanol at 60℃; for 3h;
1 Example 1: Synthesis of Compound 2a
Compound 1a (1 mmol, 119 mg), [HDBN+][TFE-] (6 mmol, 1.35 g) was added to a 10 ml round bottom flask. In a CO2 environment, the reaction is heated to 60°C for 3 hours, and the reaction is stopped. After the temperature is cooled to room temperature, a saturated aqueous NH4Cl solution is added. Adjust the pH to neutral, extract three times with 20ml CH2Cl2, collect the CH2Cl2 solution and dry it over anhydrous sodium sulfate. After filtration, the solution was removed by evaporation under reduced pressure, and the resulting solid was separated by silica gel column chromatography (eluent: CH2Cl2:CH3OH=15:1).155 mg of white solid compound 2a, yield 95%.
95%
With 1,5-diazabicyclo[4.3.0]non-5-ene 2,2,2-trifluoroethanol at 60℃; for 3h; Green chemistry;
General experimental procedure
2-Amino-nicotinonitrile 1 (1.0mmol), and [HDBN+][TFE-] (6.0mmol) were loaded into a 10mL glass reaction tube equipped with a magnetic stirrer. The air in the reactor was replaced by CO2. Then, the reactor was stirred at 60°C for 3h under CO2 using a balloon. Upon reaction completion, the reaction was cooled to room temperature and quenched with a saturated ammonium chloride solution. The mixture was filtered to afford the crude product, which was purified by chromatography (silica gel, methanol/dichloromethane=1/20) to give compound 2 as a white solid (95%). 1H NMR (400MHz, DMSO-d6): δ=11.70 (s, 1H), 11.51 (s, 1H), 8.60 (d, J=2.4 Hz, 1H), 8.26 (d, J=4.0 Hz, 1H), 7.25 (m, 1H); 13C NMR (100 MHz, DMSO-d6): δ=162.94, 155.09, 152.91, 150.96, 136.92, 119.41, 110.43; HRMS (ESI): [M+H+] calcd. for [C7H6N3O2]+, 164.0460; found, 164.0462.
59%
With tetrabutyl ammonium fluoride In dimethyl sulfoxide at 110℃; for 24h; Autoclave;
4.4. Synthesis of quinazoline-2,4(1H,3H)-diones 5 from 2-aminobenzonitriles 4 and CO2: general procedure
General procedure: Table 5: To a DMSO-d6 solution (1 mL) of 2-aminobenzonitrile 4a (1 mmol) in a stainless steel autoclave was added a catalyst (0.01 mmol) under an argon atmosphere. The autoclave was sealed, heated at 110°C and then pressurized with CO2 of 2 MPa. The cyclization reaction of 4a proceeded by the magnetic stirring of the resulting mixture at 110°C for 3 h. After the reaction the autoclave was cooled in an ice bath and depressurized. The chemical yield of quinazoline-2,4(1H,3H)-dione 5a was determined by integrating 1HNMR with reference to an internal standard (3,5-dimethoxybenzylalcohol), which was added to the reaction mixture. Table 6: DMSO solution (6 mL) of 4 (6 mmol) was treated for the carboxylative cyclization of 4 with CO2 according to the procedure of Table 5. After the reaction, the autoclave was cooled in an ice bath and depressurized, and the reaction mixture was added to water (60 mL). The precipitation was collected by filtration, washed with water and diethyl ether, and then dried in vacuo at 35°C for 15 h to give the pure product 5.
54%
With {Eu[N(SiMe3)2](μ-O:κ2-C6H5C(O)NC6H3(iPr)2)(THF)}2; 1,8-diazabicyclo[5.4.0]undec-7-ene In dimethyl sulfoxide at 100℃; for 24h; Schlenk technique;
Multi-step reaction with 3 steps
1: acetic acid / water / 25 °C / Green chemistry
2: sodium hydroxide / water / 4 h / Green chemistry
3: hydrogenchloride / water / pH < 1 / Green chemistry
Typical Experimental Procedure
General procedure: pH of the reaction mixture was carefully adjusted to pH <1 with concentrated HCl, affording a white precipitate. After filtration and washing with water until pH 7 was attained, the desired products were obtained. The structures of the products were confirmed by spectral analyses, and the data agreed well with those reported in the literature.
N4-(4-cyanobenzyl)-N2-isopropylpyrido[2,3-d]pyrimidine-2,4-diamine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
Multi-step reaction with 3 steps
1: trichlorophosphate; phosphorus pentachloride / 135 °C
2: tetrahydrofuran / 3 h / 20 °C
3: 1,4-dioxane / 48 h / 120 - 150 °C
Multi-step reaction with 3 steps
1: phosphorus pentachloride; trichlorophosphate / 6 h / 120 °C / Inert atmosphere
2: triethylamine / tetrahydrofuran / 20 °C
3: 1,4-dioxane / 48 h / 120 °C
N-(5-((4-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)pyrido[2,3-d]pyrimidin-2-yl)amino)-2-(dimethylamino)-4-methoxyphenyl)propionamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
Multi-step reaction with 6 steps
1: trichlorophosphate / 6 h / 160 °C
2: potassium carbonate / methanol; water / 6 h / 20 °C
3: toluene-4-sulfonic acid / methanol / 6 h / 90 °C
4: potassium carbonate / N,N-dimethyl-formamide / 4 h / 50 °C
5: iron; ammonium chloride / ethanol; water / 4 h / 70 °C
6: triethylamine / N,N-dimethyl-formamide / 10 h / 0 °C
4-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-N-(4-fluoro-2-methoxy-5-nitrophenyl)pyrido[ 2,3-d]pyrimidin-2-amine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
Multi-step reaction with 3 steps
1: trichlorophosphate / 6 h / 160 °C
2: potassium carbonate / methanol; water / 6 h / 20 °C
3: toluene-4-sulfonic acid / methanol / 6 h / 90 °C
N1-(4-(6,7-dihydrothiophene[3,2-c]pyridin-5-(4H)-yl)pyrido[2,3-d]pyrimidin-2-yl)-2-methoxy-N4,N4-dimethyl-5-nitrophenyl-1,4-diamine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
Multi-step reaction with 4 steps
1: trichlorophosphate / 6 h / 160 °C
2: potassium carbonate / methanol; water / 6 h / 20 °C
3: toluene-4-sulfonic acid / methanol / 6 h / 90 °C
4: potassium carbonate / N,N-dimethyl-formamide / 4 h / 50 °C
N1-(4-(6,7-dihydrothiopheno[3,2-c]pyridin-5(4H)-yl)pyrido[2,3-d]pyrimidin-2-yl)-2-methoxy-N4,N4-dimethyl-5-nitrobenzene-1,4-diamine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
Multi-step reaction with 5 steps
1: trichlorophosphate / 6 h / 160 °C
2: potassium carbonate / methanol; water / 6 h / 20 °C
3: toluene-4-sulfonic acid / methanol / 6 h / 90 °C
4: potassium carbonate / N,N-dimethyl-formamide / 4 h / 50 °C
5: iron; ammonium chloride / ethanol; water / 4 h / 70 °C
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