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CAS No. : | 695-34-1 | MDL No. : | MFCD00006321 |
Formula : | C6H8N2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | ORLGLBZRQYOWNA-UHFFFAOYSA-N |
M.W : | 108.14 | Pubchem ID : | 1533 |
Synonyms : |
Ascensil
|
Num. heavy atoms : | 8 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.17 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 1.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 33.61 |
TPSA : | 38.91 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.56 cm/s |
Log Po/w (iLOGP) : | 1.24 |
Log Po/w (XLOGP3) : | 0.56 |
Log Po/w (WLOGP) : | 0.98 |
Log Po/w (MLOGP) : | 0.54 |
Log Po/w (SILICOS-IT) : | 1.14 |
Consensus Log Po/w : | 0.89 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.42 |
Solubility : | 4.13 mg/ml ; 0.0382 mol/l |
Class : | Very soluble |
Log S (Ali) : | -0.95 |
Solubility : | 12.1 mg/ml ; 0.112 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -1.99 |
Solubility : | 1.11 mg/ml ; 0.0103 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.2 |
Signal Word: | Danger | Class: | 8,6.1 |
Precautionary Statements: | P260-P264-P270-P271-P273-P280-P301+P310+P330-P301+P330+P331-P303+P361+P353-P304+P340+P310-P305+P351+P338+P310-P361+P364-P403+P233-P405-P501 | UN#: | 2923 |
Hazard Statements: | H301+H311+H331-H314-H412 | Packing Group: | Ⅱ |
GHS Pictogram: |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87.2% | at 150℃; for 1 h; | A mixture of 2-amino-3-chloro-4-methylpyridine 0.96 g (0. 0067πο1) and benzoic acid, 1.83 g (0.015 mol) was added, copper powder was added, reacted at 150 ° C for 1 h, and the reaction solution was added to water , Adding the decolorizer, adjusting the pH of the filtered solution to pH 9, filtering and drying the filter cake to obtain 0.65 g of crude 2-amino-4-methylpyridine as a yellow solid, the yield was 89.3percent. 2-amino-4-methylpyridine crude 0.65g dissolved in dilute hydrochloric acid solution to the crude product completely dissolved to obtain a salt solution, adding ethyl acetate to the salt solution to extract the water phase, slowly adding sodium bicarbonate to the aqueous phase Solution to pH 9, the solid was completely precipitated, filtered, and the filtrate was washed with distilled water and dried in vacuo to give 0.53 g of 2-amino-4-methylpyridine as a pale yellow solid with a yield of 81.5percent and a purity of 99.2percent 95-96. 6.38 (d, lH, J = 2.3 Hz); 6.34 (dd, lH, r, r = J = 5.7 Hz, 2.3 Hz); 3.46 (s, 2H); 2.39 (s, 3H);ESI-MS m / z (percent): 109.1 ([M + l] +) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | Stage #1: With sulfuric acid; sodium nitrite In water at 0 - 95℃; for 2.25 h; Stage #2: With sodium hydroxide In water at 20℃; |
Synthesis of intermediate V-a: 4-Methyl-pyridin-2-olIntermediate V-a was prepared using the method of Adger et al, in J. Chem. Soc. Perkin Trans. 1, 1988, p2791 -2796. A 1 L flask containing water (240 mL) was treated with cone. H2S04 (32 mL) and cooled to 0°C then treated with the 2-amino-4-picoline in one portion (30 g, 277 mmol). A solution of NaN02 (20.6 g, 299 mmol) in water (40 mL) was added dropwise over 1 h such that the internal temperature never rose above 5°C. The reaction was stirred at 0°C for lh then heated to 95°C and after 15 min at this temperature cooled to room temperature. The solution was taken to pH 6-7 with 50percent NaOH aq (exotherm) and extracted whilst hot with EtOAc (4 x 120 mL). The combined organics were dried (MgS04), filtered and evaporated to afford a beige crystalline solid (24.5 g, 81percent) of intermediate V-a.1H NMR (300 MHz, DMSO-d6) δ 1 1.31 (s, 1H), 7.23 (d, J= 6.7 Hz, 1H), 6.10 (s, 1H), 6.00 (dd, J= 6.7, 1.2 Hz, lH), 2.10 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With sodium nitrite In hydrogenchloride | a) 2-Chloro-4-methylpyridine Sodium nitrite (13.88 g, 200 mmole) was added slowly at 0° C. to a solution of 2-amino-4-picoline (15.0 g, 139 mmole) in conc. HCl (200 mL). The reaction mixture was allowed to warm to RT and was stirred for 16 hr, then was poured onto ice (500 g). The pH was adjusted to 8.0 with conc. NH4OH, and the mixture was extracted with ether (3*300 mL). The combined ether layers were washed sequentially with H2O (2*200 mL) and brine (200 mL). Drying (MgSO4) and concentration gave the title compound (10.3 g, 58percent) as a faintly yellow oil: MS (ES) m/e 127.8 (M+H)+. |
229.3 g | With hydrogenchloride; sodium nitrite In water at 20℃; Industrial scale | Firstly, 188 g of 2-amino-4-methylpyridine was fed into a round bottom flask, and then 250 g of sodium nitrite was added into a round bottom flask. Subsequently, 150 g of hydrogen chloride was continuously fed and the reaction temperature was controlled at 20 ° C.The reaction produces primiparous,The crude steamed isolated 229.3 g of 2-chloro-4-methylpyridine (content of 99percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69.5% | Stage #1: With hydrogenchloride In methanol at 10 - 30℃; for 1.5 h; Stage #2: at 20 - 30℃; for 13 h; Stage #3: With sodium hydroxide In water at 30℃; |
(a); Into a 2L four-necked flask equipped a stirrer, a thermometer and a gas introduction tube (inlet), 324 g (3.00 mol) of 2-amino-4-methylpyridine and 485 g of methanol were charged and mixed for dissolution, and while keeping the temperature in the system at from 10 to 30°C, 361.4 g (9.90 mol) of hydrogen chloride gas was introduced over a period of one and a half hours. Then, in a 2L four-necked flask equipped with a stirrer, a thermometer, a dropping funnel and an introduction tube (outlet) equipped with a bubble counter having a gas generation apparatus and a diazotization apparatus connected, 414 g (6.00 mol) of sodium nitrite, 211 g (6.60 mol) of methanol and 454 g of water were mixed, and 812.4 g (3.15 mol) of a 38percent sulfuric acid aqueous solution was dropwise added over a period of 5 hours while keeping the temperature in the system at from 20 to 30°C. In the methyl nitrite generation apparatus, simultaneously with dropwise addition of the 38percent sulfuric acid aqueous solution, methyl nitrite gas in an equivalent amount was generated and introduced to the diazotization apparatus through the bubble counter. Further, for diazotization, the reaction apparatus was cooled with water so that the temperature in the system would be kept at from 20 to 30°C. After completion of the introduction of the methyl nitrite gas, stirring was carried out at the same temperature for 13 hours and the reaction was completed. After methanol was distilled off under reduced pressure, 648 g of water was charged, and 518 g of a 40percent sodium hydroxide aqueous solution was dropwise added at 30°C or below to adjust the pH in the system to 12. The formed oil was extracted with 910 g of diethyl ether, the aqueous layer was separated out, and the solvent was distilled off under reduced pressure to obtain 375.3 g of an oil. The oil (crude product) had a composition comprising 70.7percent (yield: 69.5percent) of 2-chloro-4-methylpyridine, 26.6percent (yield: 27.2percent) of 2-methoxy-4-methylpyridine and 2.6percent of 2-amino-4-methylpyridine. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | Stage #1: With hydrogen bromide; bromine In water at -20 - -15℃; for 3 h; Stage #2: With sodium nitrite In water at 20℃; for 3 h; Stage #3: With sodium hydroxide In water at 0℃; |
To a solution of 2-amino-4-methylpyridine (120 g, 1.1 mol) in 48percent HBr (1.5 L) at -20° C. was added bromine (160 mL, 3.11 mol) dropwise. The reaction mixture was stirred for 3 h at -15° C. to -20° C. To the above mixture was added portionwise an aqueous solution of NaNO2 (204 g, 2.95 mol). The reaction mixture was then allowed to warm to RT over a period of 3 h. A 20percent aqueous NaOH (1.2 Kg of NaOH in 2 L water) solution was added and the pH was adjusted to 12 maintaining the temperature at 0° C. The reaction mixture was extracted with diethyl ether (3.x.250 mL), washed with water, brine and dried. The solvent was removed and purified by fractional distillation to afford 2-bromo-4-methylpyridine (164 g, 86percent) as pale yellow liquid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69.5% | Stage #1: With hydrogenchloride In methanol at 10 - 30℃; for 1.5 h; Stage #2: at 20 - 30℃; for 13 h; Stage #3: With sodium hydroxide In water at 30℃; |
(a); Into a 2L four-necked flask equipped a stirrer, a thermometer and a gas introduction tube (inlet), 324 g (3.00 mol) of 2-amino-4-methylpyridine and 485 g of methanol were charged and mixed for dissolution, and while keeping the temperature in the system at from 10 to 30°C, 361.4 g (9.90 mol) of hydrogen chloride gas was introduced over a period of one and a half hours. Then, in a 2L four-necked flask equipped with a stirrer, a thermometer, a dropping funnel and an introduction tube (outlet) equipped with a bubble counter having a gas generation apparatus and a diazotization apparatus connected, 414 g (6.00 mol) of sodium nitrite, 211 g (6.60 mol) of methanol and 454 g of water were mixed, and 812.4 g (3.15 mol) of a 38percent sulfuric acid aqueous solution was dropwise added over a period of 5 hours while keeping the temperature in the system at from 20 to 30°C. In the methyl nitrite generation apparatus, simultaneously with dropwise addition of the 38percent sulfuric acid aqueous solution, methyl nitrite gas in an equivalent amount was generated and introduced to the diazotization apparatus through the bubble counter. Further, for diazotization, the reaction apparatus was cooled with water so that the temperature in the system would be kept at from 20 to 30°C. After completion of the introduction of the methyl nitrite gas, stirring was carried out at the same temperature for 13 hours and the reaction was completed. After methanol was distilled off under reduced pressure, 648 g of water was charged, and 518 g of a 40percent sodium hydroxide aqueous solution was dropwise added at 30°C or below to adjust the pH in the system to 12. The formed oil was extracted with 910 g of diethyl ether, the aqueous layer was separated out, and the solvent was distilled off under reduced pressure to obtain 375.3 g of an oil. The oil (crude product) had a composition comprising 70.7percent (yield: 69.5percent) of 2-chloro-4-methylpyridine, 26.6percent (yield: 27.2percent) of 2-methoxy-4-methylpyridine and 2.6percent of 2-amino-4-methylpyridine. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With dihydrogen peroxide; 1-butylpyridinium bromide; toluene-4-sulfonic acid In 1,2-dimethoxyethane at 80℃; for 24 h; Schlenk technique; Inert atmosphere; Green chemistry | General procedure: To a mixture of 2-aminopyridine (0.5 mmol, 1 equiv), p-TSA (0.4 mmol,0.8 equiv), 1-butylpyridinium bromide (1.5 mmol, 3 equiv) in a 50 mL Schlenk tube were added 1,2-dimethoxyethane (2 mL) under air. Then H2O2 (1.2 mmol, 2.4 equiv) was added. The mixture was stirred at 80°C for 24 h. And then the mixture was purified by silica gel column chromatography (petroleum ether/ethyl acetate) to give the products. |
23% | With sodium hydroxide; bromine In acetic acid | EXAMPLE 41 STR43 2-Amino-5-bromo-4-methylpyridine To a solution of 2-amino-4-picoline (20 g, 0.185 mol) in glacial acetic acid (185 mL) was added bromine (12.5 mL, 0.243 mol) dropwise with stirring while maintaining the internal temperature between 15-20° C. by cooling in an ice bath. After the addition was completed, the reaction was stirred for 1 h. The resulting solid was filtered, washed with water, and treated with dilute aqueous sodium hydroxide. The remaining white solid was filtered, washed with water and then hexane. Recrystallization from diethyl ether-cyclohexane afforded the title compound; yield 8.1 g (23percent). 1 H NMR (400 MHz, CD3 OD): δ 2.25 (s, 3H), 6.51 (s, 1H), 7.89 (s, 1H). Mass spectrum (FAB): m/e=187 (M). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.9% | Stage #1: With nitric acid In water at 40℃; for 4 h; Stage #2: for 2 h; Reflux |
(2) 2-Amino-4-methylpyridine was mixed with water,Heat to 40°C, add Fe-Mn-Mo-TiO catalyst,After stirring, dilute nitric acid is added dropwise.Stir the reaction for 4h,After falling to room temperature,filter,The filtrate was adjusted to pH 9,After adding methanol,After heating and refluxing for 2h,Vacuum distillation to remove methanolMultiple extractions with dichloromethane,Combine the organic phase,Distillation under reduced pressure to remove the dichloromethane,Preparation of 2-aminopyridine-4-carboxylic acid methyl ester.Fe(NO3)3, in step (1)MnCl2,The molar ratio of molybdenum was 4:7:1, the mass ratio of Fe(NO3)3 to nano-TiO2 particles was 1:1, and the molar ratio of NaOH and Na2CO3 was 4:1.In step (2), the mass ratio of 2-amino-4-methylpyridine to Fe-Mn-Mo-TiO catalyst is 11:2.The mass concentration of nitric acid was 30percent, the molar ratio of 2-amino-4-methylpyridine to nitric acid was 1:1.5, and the molar ratio of 2-amino-4-methylpyridine to methanol was 1:1.The methyl 2-aminopyridine-4-carboxylate was prepared with a purity of 99.4percent and a yield of 93.9percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46.6% | Stage #1: at 0 - 50℃; for 24 h; Stage #2: Cooling with ice |
Example 9: Synthesis of the 2-(1-ethyleneimine)-4-carbamoyl-5-nitropyridine (compound VI) [Show Image][Show Image] The reagents used was ( i ) HNO3/H2SO4; ( ii ) NaNO2; (iii) POCl3; (iv) Na2Cr2O7; (v) SOCl2/DMF, followed by NH4OH; (vi) aziridine.Synthesis of the compound 30 A concentrated sulphuric acid (240mL) was cooled in an ice bath, the starting material compound 29 (50g, 0.462 mol) was slowly added and cooled to 0°C, 55 mL of an mixture in volumetric ratio of 1:1 of a concentrated sulphuric acid (98percent) and a concentrated nitric acid (72percent) was slowly added and heated slowly to 50°C, and the reaction was completed after 24 hours. The reaction solution was introduced into 2 L of ice-water, followed by adjusting pH to 7 by adding strong aqua, and filtered. The filter cake was dried, yielding 54g of the crude product. The above mixture was subject to wet distillation to remove 4-methyl-3-nitro-2-aminopyridine, then filtered and recrystallized in ethanol (95percent) to obtain 33 g of the compound 30 with a melting point of 220-222°C(M.P. 220-222°C was reported in the reference [J.O.C. , 1955, 20, 1729-1731]). The yield was 46.6percent. |
37.08% | at -5 - 50℃; for 24 h; | A solution of 150 ml of concentrated H2SO4 was charged into a 500 ml round bottom flask and placed in a low temperature cold bath at -5 ° C. After 20 minutes, 50 g of raw material 22 (2-amino-4-methylpyridine) was added in portions and the solution was gradually purified from the colorless clear solution Into a yellow viscous solution, the whole process to keep the internal temperature does not exceed 0 .Preparation of 34ml concentrated H2SO4With 34ml concentrated HNO3Of the mixed acid in -5 in the pre-cooling, through the constant pressure dropping funnel slowly added to the reaction solution, keep the temperature does not exceed 0 , drop Bi, the reaction at room temperature for 20min, transferred to the oil bath slowly heated Heated to 50 , resulting in a large number of bubbles, the reaction liquid color gradually deepened into brown.After the bubble was no longer produced, the reaction was continued at 50 ° C.TLC monitoring reaction, 24 hours after the reaction is complete, stop the reaction.The reaction solution was slowly added to the beaker with ice-water stirring to avoid exotherm. The pH was adjusted to pH (about 8) with NaOH solution. A large amount of mud-yellow solid was precipitated, washed and washed with water to neutral, To the culture dish, dried under an infrared lamp, and dried at 50 ° C under reduced pressure for 3 hours to obtain 41.61 g of a crude yellow solid.After recrystallization with EA, the insoluble impurities were removed by hot filtration, and a portion of the solvent was removed by spin-spinning and then recrystallized from EA. The crystals were crystallized at room temperature and filtered to give an orange solid of 18.54 g and a yield of 37.08percent. |
27% | Stage #1: at 0 - 100℃; for 22 h; Stage #2: With sodium hydroxide In water at 20℃; |
Concentrated sulfuric acid (120 mL) was cooled in an ice bath at 0°C. 2-Amino-4-methylpyridine (25.0 g, 230 mmol) was added portionwise. A mixture of concentrated sulfuric acid (18 mL) and concentrated nitric acid (17.5 mL) was added with addition funnel over 1 h, maintaining the temperature at 0°C. The reaction mixture was then warmed to room temperature over 4 h. After 15 h, the reaction mixture was heated at 60°C for 1 h, and then at 100°C for 1 h. The reaction mixture was poured over ice and adjusted to pH 4-5 with 6 N aqueous sodium hydroxide. The 3-regioisomer was removed by steam distillation (9.11 g, 26percent). The remaining residue was extracted with methylene chloride and dried over sodium sulfate, and the solvent was evaporated. The dark yellow solid was crystallized from acetonitrile and methanol to give 2-amino-4-methyl-5- nitropyridine (9.53 g, 27percent) as a dark yellow solid: 1H NMR (300 MHz, CD30D) 82.53 (3H, s), 6.39 (lH, s), 8.76 (lH, s). |
18% | Stage #1: at 20 - 50℃; for 7.75 h; |
Ste 1: 4-methyl-5-nitropyridin-2-amineTo the solution of 4-methylpyridin-2-amine (5.80 g, 53.6 mmol) in COW.H2SO4 (8 mL), the mixture of sulfuric acid (4.00 mL, 75 mmol) and nitric acid (4.05 mL, 91 mmol) was added at 5-20 °C during 15 minutes. The mixture was stirred at room temperature for 30 minutes, and then heated to 35-40 °C for 2 hours, 50 °C for 5 hours. The mixture was poured onto ice, adjusted pH to 9 with con. NH4OH. The precipitates were collected and purified with Column Chromatography (EtOAc : petrol ether = 1:3) to give the desired product (1.5 g, 18percent).1H NMR (DMSO- ): δ 8.75 (1H, s), 7.27 (2H, s), 6.31 (1H, s), 2.49 (3H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
27% | at 0 - 70℃; for 4 h; | The syntheses of several 2-aminonitropyridines were described previously by Talik and Talik [29]. Their methods were applied in the syntheses of I–III compounds using commercially available 2-amino-4-methylpyridine (Fluka, >99percent). These compounds were obtained as follows: 25 g of appropriate 2-amino-4-methylpyridine were dissolved in 125 cm3 of concentrated H2SO4 (Fluka, 96percent). The reaction mixture was cooled under intensive stirring to 0 °C by adding ice mixed with NaCl. Subsequently, 37.5 cm3 of HNO3 (Chempur, 65percent, d = 1.4 g/cm3) were added in small portions keeping the temperature below 10 °C. Then the mixture was stirred for 1.5 h with continuous cooling, and kept at ambient temperature for 1 h. Next, the reaction mixture was heated in a water bath for half an hour at 40 °C, 1 h in the temperature range 60–70 °C and half an hour in a boiling water bath. Then, the whole reaction mixture was cooled to ambient temperature, poured on ice and neutralized with ammonia to a slightly alkaline pH. The solid reaction product was filtered off under vacuum. Two nitro isomers (3 and 5) were separated by steam distillation. More volatile 3- nitro isomer (I) was distilled off and condensed as a pure compound (obtained after drying 10 g), while residual 5-nitro isomer (III) was filtered off and crystallized from water (with H2SO4 and active carbon added initially for dissolving the compound and removing impurities). After neutralization, filtering off and drying, about 15 g of 5-nitro isomer (III) was obtained. The 2-amino-4-methyl-3,5-dinitropyridine (II) was obtained from 2-amino-4-methyl-5-nitropyridine (III) by a similar procedure (nitration and rearrangement to dinitropyridines). The residues were purified by crystallization from water to give 2-amino-4-methyl-3-nitropyridine, I (Yield: (27percent (10 g), m.p. 134(1) °C), 2-amino-4-methyl-3,5-dinitropyridine, II (Yield: 80percent (10.4 g), m.p. 197(1) °C) and 2-amino-4-methyl-5-nitropyridine, III (Yield: 40percent (15 g), m.p. 218(1) °C), respectively. Melting points were determined using a Köfler apparatus. The chemical composition of the obtained compounds was checked using the Carlo Erba Analyser, Model 1104. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
27% | at 0 - 70℃; for 4 h; | The syntheses of several 2-aminonitropyridines were described previously by Talik and Talik [29]. Their methods were applied in the syntheses of I–III compounds using commercially available 2-amino-4-methylpyridine (Fluka, >99percent). These compounds were obtained as follows: 25 g of appropriate 2-amino-4-methylpyridine were dissolved in 125 cm3 of concentrated H2SO4 (Fluka, 96percent). The reaction mixture was cooled under intensive stirring to 0 °C by adding ice mixed with NaCl. Subsequently, 37.5 cm3 of HNO3 (Chempur, 65percent, d = 1.4 g/cm3) were added in small portions keeping the temperature below 10 °C. Then the mixture was stirred for 1.5 h with continuous cooling, and kept at ambient temperature for 1 h. Next, the reaction mixture was heated in a water bath for half an hour at 40 °C, 1 h in the temperature range 60–70 °C and half an hour in a boiling water bath. Then, the whole reaction mixture was cooled to ambient temperature, poured on ice and neutralized with ammonia to a slightly alkaline pH. The solid reaction product was filtered off under vacuum. Two nitro isomers (3 and 5) were separated by steam distillation. More volatile 3- nitro isomer (I) was distilled off and condensed as a pure compound (obtained after drying 10 g), while residual 5-nitro isomer (III) was filtered off and crystallized from water (with H2SO4 and active carbon added initially for dissolving the compound and removing impurities). After neutralization, filtering off and drying, about 15 g of 5-nitro isomer (III) was obtained. The 2-amino-4-methyl-3,5-dinitropyridine (II) was obtained from 2-amino-4-methyl-5-nitropyridine (III) by a similar procedure (nitration and rearrangement to dinitropyridines). The residues were purified by crystallization from water to give 2-amino-4-methyl-3-nitropyridine, I (Yield: (27percent (10 g), m.p. 134(1) °C), 2-amino-4-methyl-3,5-dinitropyridine, II (Yield: 80percent (10.4 g), m.p. 197(1) °C) and 2-amino-4-methyl-5-nitropyridine, III (Yield: 40percent (15 g), m.p. 218(1) °C), respectively. Melting points were determined using a Köfler apparatus. The chemical composition of the obtained compounds was checked using the Carlo Erba Analyser, Model 1104. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
21.2% | Stage #1: at 0 - 50℃; for 24 h; Stage #2: Cooling with ice |
Example 1: Preparation of 2-(1-ethyleneimine)-4-carbamoyl-3-nitropyridine (the compound II) [Show Image] The reagents used is ( i ) HNO3/H2SO4; (ii) NaNO2; (iii) POCl3; (iv) K2Cr2O7; ( v ) SOCl2, followed by NH4OH; (vi) aziridine.Synthesis of the compound 8 A concentrated sulphuric acid (240mL) was cooled in an ice bath, the starting material compound 7 (50g, 0.462 mol) was slowly added and cooled to 0°C, 55 mL of a mixture in volumetric ratio of 1:1 of a concentrated sulphuric acid (98percent) and a concentrated nitric acid (72percent) was slowly added, then and heated slowly to 50°C, and the reaction was completed after 24 hours. The reaction solution was introduced in to 2 L ice-water, adjusted to pH=7 by adding strong aqua, and filtered. The filter cake was dried, yielding 54g of the crude product. The above filtrate mixture was subject to wet distillation, the resulted bright yellow liquid was subject to extraction with ethyl acetate and recrystallization in ethanol, resulting in 15 g compound 8 with a melting point of 136.1-136.4 °C (ethanol), or 135.4-135.7 °C (water)(M.P. 140 °C was reported in the reference [J. Chem. Soc. 1954, 2248-2451]). The yield is 21.2percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With bromine In sulfuric acid | a) Preparation of 2-Amino-3,5-dibromo-4-methylpyridine To a solution of 2-amino-4-methylpyridine(30.0 g, 0.277 mol) in 72percent sulfuric acid(130 ml) was stirred with addition of bromine(21.5 ml, 0.416 mol) at 0° C. The mixture was then allowed to warm to 25° C. for 18 hrs. The reaction was then poured into ice and the ph was adjusted to 10 with 50percent NaOH. The desired product precipitated out of solution and the mixture was filtered. The filtrate was extracted with methylene chloride and the organic layer was dried with MgSO4. The combined solids were purified by flash chromatography(2percent MeOH/CH2Cl2) to give the desired product(42.7 g, 58percent). 1H NMR (CDCl3): δ 8.08 (s, 1H), 4.95 (bs, 2H), 2.51 (s, 3H). |
54% | Stage #1: at 0℃; for 2 h; Heating / reflux Stage #2: With sodium hydroxide In water |
EXAMPLE 20 Preparation of 2-Bromo-N-((R)-3-{4-[(4-methoxy-phenyl)-(4-methyl-pyridin-3-ylmethyl)-amino]-piperidin-1-yl}-butyl)-4-methyl-nicotinamide Bromine (1.9 mL, 37.0 mmol) was added dropwise to a slurry of 2-amino-4-picoline (4.00 g, 37.0 mmol) in fuming sulfuric acid (20 mL) at 0° C. The resulting red/brown mixture was stirred at reflux for 2 h and then poured into ~200 g ice to give a yellow slurry. 10N NaOH was added slowly to the mixture until pH~12 and then the mixture was extracted with CH2Cl2 (3*50 mL), dried (Na2SO4), filtered and concentrated in vacuo to yield 3,5-dibromo-4-methyl-pyridin-2-ylamine (5.35 g, 54percent) as a pale orange solid. 1H NMR (CDCl3) δ 2.51 (s, 3H), 4.94 (br s, 2H), 8.05 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With sulfuric acid; iodine; acetic acid; periodic acid In water at 80℃; for 6 h; | To a stirred solution of 4-methyl-pyridin-2-ylamine (30g, 278mmol, 1 eq) in acetic acid (167ml_) was added periodic acid (12.7g, 55.6mmol, 0.2eq) followed by addition of sulphuric acid (4.8ml_, 90.8mmol, 0.34eq), water (33.3ml_) and iodine (28.7g, 1 1 1 .1 mmol, 0.4eq) at room temperature. Resulting reaction mixture was heated at 80°C for 6 hours. After complete consumption of starting material, reaction mixture was cooled and poured into sodium thiosulfate solution (200ml_), reddish oil was settled down at the bottom. Reaction mixture was decanted from reddish oil and filtrate was basified with 50percent sodium hydroxide solution (100ml_), yellow colored solid was formed. Resulting solid was extracted with diethyl ether (2x200 mL) and dried over sodium sulfate. Organic layer was concentrated under reduced pressure to afford brown semi solid (60g, crude). Crude was purified by column chromatography using silica gel (100-200 mesh). Desired compound was eluted at 15percent EtOAc in hexane to get title compound as faint brown solid (50.7g, 78percent). H NMR (400 MHz, CDCI3)8: 2.27 (s, 3H), 4.46 (bs, 2H), 6.44 (s, 1 H), 8.24 (s, 1 H). |
[ 199296-51-0 ]
4-(Aminomethyl)pyridin-2-amine
Similarity: 0.95
[ 199296-51-0 ]
4-(Aminomethyl)pyridin-2-amine
Similarity: 0.95