* 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.
2-Chloro-3,5-dinitropyridine (4.98 g, 24.46 mmol) was dissolved in ethanol (500 mL) and 5percent palladium on carbon (3.74 g, 0.75 g/g substrate) was added. The mixture was hydrogenated at 25° C. under 50 psi of hydrogen for 18 hrs. The mixture was filtered through celite to remove the catalyst and concentrated under reduced pressure. Purification (silica gel, 20:2:1 CHCl3/MeOH/NH4OH, followed by 12:2:1 CHCl3/MeOH/NH4OH) gave 3,5-diaminopyridine (2.27 g, 85percent) as a brown solid. 1H (CD3OD) δ 7.32 (d, 2H, J=2 Hz), 6.45-6.43 (m, 1H).
Reference：
[1] Patent: US6750348, 2004, B1, . Location in patent: Page column 113
[2] Recueil des Travaux Chimiques des Pays-Bas, 1953, vol. 72, p. 569,573
[3] Recueil des Travaux Chimiques des Pays-Bas, 1953, vol. 72, p. 569,573
[4] Recueil des Travaux Chimiques des Pays-Bas, 1953, vol. 72, p. 569,573
[5] Patent: US5668157, 1997, A,
2
[ 4663-99-4 ]
[ 4318-78-9 ]
Yield
Reaction Conditions
Operation in experiment
61%
With bromine; sodium hydroxide In water at 0 - 75℃; for 7.25 h; Schlenk technique; Inert atmosphere
The following Hofmann rearrangement was carried out according to a modified patent procedure.[39] Pyridine-3,5-dicarboxamide 45 (3.54 g, 21.4 mmol) was added to aqueous 4 M NaOH (18 mL). To this mixture was added a solution of bromine (2.65 mL, 8.27 g,51.9 mmol Br2) in aqueous 4 M NaOH (53 mL) at 0 °C dropwise over 15 min. The mixture was stirred at RT for 1 h until it turned to a clear yellow solution and was heated at 75 °C for 6 h. The now dark brown solution was washed with diethyl ether (50 mL) to remove by products and submitted to a continuous extraction with ethyl acetate (150 mL) for 3 d. Thes olvent evaporated in vacuo and pyridine-3,5-diamine 29 (1.43 g, 13.0 mmol, 61 percent) was obtained as a greenish brown solid (Rf = 0.14, CH2Cl2 / MeOH 10 : 1).
Reference：
[1] Journal of Organic Chemistry, 2012, vol. 77, # 15, p. 6653 - 6656
[2] Recueil des Travaux Chimiques des Pays-Bas, 1955, vol. 74, p. 1062,1068
[3] Chemische Berichte, 1936, vol. 69, p. 1534,1536
[4] Recueil des Travaux Chimiques des Pays-Bas, 1936, vol. 55, p. 122,126
[5] Patent: CH174873, 1933, ,
[6] Chemistry - A European Journal, 2000, vol. 6, # 15, p. 2830 - 2846
4
[ 1159200-50-6 ]
[ 4318-78-9 ]
Reference：
[1] Journal of Organic Chemistry, 2009, vol. 74, # 11, p. 4246 - 4251
5
[ 5418-51-9 ]
[ 4318-78-9 ]
Reference：
[1] Recueil des Travaux Chimiques des Pays-Bas, 1953, vol. 72, p. 569,573
[2] Recueil des Travaux Chimiques des Pays-Bas, 1953, vol. 72, p. 569,573
[3] Recueil des Travaux Chimiques des Pays-Bas, 1953, vol. 72, p. 569,573
6
[ 2980-33-8 ]
[ 4318-78-9 ]
Reference：
[1] Recueil des Travaux Chimiques des Pays-Bas, 1953, vol. 72, p. 569,573
[2] Recueil des Travaux Chimiques des Pays-Bas, 1953, vol. 72, p. 569,573
[3] Recueil des Travaux Chimiques des Pays-Bas, 1953, vol. 72, p. 569,573
7
[ 940-06-7 ]
[ 4318-78-9 ]
Reference：
[1] Recueil des Travaux Chimiques des Pays-Bas, 1953, vol. 72, p. 569,573
8
[ 13250-43-6 ]
[ 4318-78-9 ]
Reference：
[1] Recueil des Travaux Chimiques des Pays-Bas, 1953, vol. 72, p. 569,573
9
[ 55106-97-3 ]
[ 4318-78-9 ]
Reference：
[1] Recueil des Travaux Chimiques des Pays-Bas, 1953, vol. 72, p. 569,573
10
[ 625-92-3 ]
[ 7758-99-8 ]
[ 4318-78-9 ]
Reference：
[1] Recueil des Travaux Chimiques des Pays-Bas, 1936, vol. 55, p. 122,126
[2] Chemische Berichte, 1936, vol. 69, p. 1534,1536
11
[ 2457-47-8 ]
[ 7758-99-8 ]
[ 4318-78-9 ]
Reference：
[1] Roczniki Chemii, 1938, vol. 18, p. 39,41[2] Chem. Zentralbl., 1939, vol. 110, # I, p. 1366
With potassium carbonate; In 1,4-dioxane; for 22.0h;Heating / reflux;
<strong>[4318-78-9]3,5-diaminopyridine</strong> (381.4 mg, 3.49 mmol) was dissolved in anhydrous 1,4-dioxane (6 mL) and K2CO3 (1.45 g, 10.5 mmol) was added, followed by ethyl chloroformate (1.0 mL, 10.5 mmol). The thick slurry was heated at reflux for 22 hrs. The solvent was removed under reduced pressure, the residue was taken up in methanol and filtered through celite. Purification (silica gel, 9:1 CH2Cl2/MeOH) gave the bis-carbamate (608 mg, 69percent) as a light brown solid. 1H (CD30D) delta 8.37 (s, 2H), 8.28-8.27 (m, 1H), 4.22 (q, 4H, J=7 Hz), 1.31 (t, 6H, J=7 Hz).
EXAMPLE A-7 3,5-Pyridinediamine, 2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl 97percent yield from 3,5-bis-(chlorocarbonyl)-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl) pyridine product of Step 6 above as a dark oil; used in further steps without purification, since this material is unstable.
With hydrogen;5%-palladium/activated carbon; In ethanol; at 25℃; under 2585.81 Torr; for 18.0h;
2-Chloro-3,5-dinitropyridine (4.98 g, 24.46 mmol) was dissolved in ethanol (500 mL) and 5percent palladium on carbon (3.74 g, 0.75 g/g substrate) was added. The mixture was hydrogenated at 25° C. under 50 psi of hydrogen for 18 hrs. The mixture was filtered through celite to remove the catalyst and concentrated under reduced pressure. Purification (silica gel, 20:2:1 CHCl3/MeOH/NH4OH, followed by 12:2:1 CHCl3/MeOH/NH4OH) gave 3,5-diaminopyridine (2.27 g, 85percent) as a brown solid. 1H (CD3OD) delta 7.32 (d, 2H, J=2 Hz), 6.45-6.43 (m, 1H).
palladium; In methanol;
Step 1 3,5-Diaminopyridine A mixture of 2-chloro-3,5-dinitropyridine (5.0 g, 0.0246 mol), methanol (150 ml) and 10percent palladium-on-carbon catalyst (0.5 g) was hydrogenated at an initial hydrogen pressure of 50 p.s.i. The mixture was filtered through celite and the filtrate concentrated to give a mixture of 3,5-diaminopyridine and 2-chloro-3,5-diaminopyridine.
With bromine; sodium hydroxide; In water; at 0 - 75℃; for 7.25h;Schlenk technique; Inert atmosphere;
The following Hofmann rearrangement was carried out according to a modified patent procedure.[39] Pyridine-3,5-dicarboxamide 45 (3.54 g, 21.4 mmol) was added to aqueous 4 M NaOH (18 mL). To this mixture was added a solution of bromine (2.65 mL, 8.27 g,51.9 mmol Br2) in aqueous 4 M NaOH (53 mL) at 0 °C dropwise over 15 min. The mixture was stirred at RT for 1 h until it turned to a clear yellow solution and was heated at 75 °C for 6 h. The now dark brown solution was washed with diethyl ether (50 mL) to remove by products and submitted to a continuous extraction with ethyl acetate (150 mL) for 3 d. Thes olvent evaporated in vacuo and pyridine-3,5-diamine 29 (1.43 g, 13.0 mmol, 61 percent) was obtained as a greenish brown solid (Rf = 0.14, CH2Cl2 / MeOH 10 : 1).
N,N'-(pyridine-3,5-diyl)bis(2,2,2-trifluoroacetamide)[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
97%
In dichloromethane; at 20℃;Inert atmosphere;
To <strong>[4318-78-9]pyridine-3,5-diamine</strong> (527 mg, 4.83 mmol, commercially available from, for example, 3B Scientific Corporation) in dichloromethane (DCM) (10 mL) was added TFAA (1.773 mL, 12.56 mmol) and the reaction stirred overnight at rt under nitrogen. Solvent was removed and the residue washed with methanol and azeotroped with DCM and dried under high vacuum overnight to give a sticky brown solid (2.2 g, yield 97percent).LCMS (Method B): Rt=0.80 min, MH+=302.0.
General procedure: This compound was synthesized by the method described in reference [18] for the synthesis of Schiff-base compounds. To a solution of <strong>[4318-78-9]3,5-diaminopyridine</strong> [IV] (0.01 mole) in absolute ethanol (10 mL) was added two molar amount of the 4-alkoxybenzaldhyde (0.02 mole) with two drops of glacial acetic acid and the mixture was refluxed at 80C for 5 hrs. After completion of reaction, the mixture was cooled and poured into the ice cold water. The solid obtained was filtered, washed with ice cold water, dried and recrystalized from ethanol. Analytical data 3,5-Di-(4-heptaoxy)benzylidineaminopyridine [VI]a Yield: 64%; m.p.: 196-198C: FTIR (nu/cm-1): 2958-2870 (CH aliphatic), 1618 (CN),1578 (CN pyridene moiety). 1HNMR (DMSO-d6), ppm: d0.91 (t, 6H, CH3),1.21-1.82 (m, 20H, CH2), 3.14 (t, 4H, CH2O), 6.41-7.60 (m, 8H, Ar-H and 3H,pyridene moiety) 8.42 (s, 2H, CHN). 13C NMR (125 MHz, CDCl3): d 14.01, 23.1,26.6, 30.0, 32.5, 34.6, 72.3, 114.1-155.8 and 162.8. MS: m/z+1=514. Anal. Calcd. for C33H43O2 N3: C, 77.19; H, 8.38; N, 8.19. Found: C, 77.25; H, 8.42; N, 8.22.
General procedure: This compound was synthesized by the method described in reference [18] for the synthesis of Schiff-base compounds. To a solution of <strong>[4318-78-9]3,5-diaminopyridine</strong> [IV] (0.01 mole) in absolute ethanol (10 mL) was added two molar amount of the 4-alkoxybenzaldhyde (0.02 mole) with two drops of glacial acetic acid and the mixture was refluxed at 80C for 5 hrs. After completion of reaction, the mixture was cooled and poured into the ice cold water. The solid obtained was filtered, washed with ice cold water, dried and recrystalized from ethanol.
General procedure: This compound was synthesized by the method described in reference [18] for the synthesis of Schiff-base compounds. To a solution of <strong>[4318-78-9]3,5-diaminopyridine</strong> [IV] (0.01 mole) in absolute ethanol (10 mL) was added two molar amount of the 4-alkoxybenzaldhyde (0.02 mole) with two drops of glacial acetic acid and the mixture was refluxed at 80C for 5 hrs. After completion of reaction, the mixture was cooled and poured into the ice cold water. The solid obtained was filtered, washed with ice cold water, dried and recrystalized from ethanol.
N-(5-aminopyridin-3-yl)-2-phenylacetamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
61%
With pyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; at 50℃; for 2.0h;
A mixture of 2-phenylacetic acid (374 mg, 2.75 mmol), pyridine-3, 5 -diamine (300 mg, 2.75 mmol) and EDCI.HC1 (580 mg, 3.02 mmol) in pyridine (5 mL) was heated at 50 C for 2 h. A black solution was formed. LCMS (Rt = 0.405 min; MS Calcd: 227.1; MS Found: 227.9 [M+H]+). The mixture was concentrated and the residue was poured into water (20 mL) and stirred for 2 minutes. The aqueous layer was extracted with ethyl acetate (20 mL x3). The combined organic layer was washed with water (30 mL x2) and brine (30 mL), dried over anhydrous Na2SC>4, filtered and concentrated. The residue was purified by Combi Flash (50% to 100% EtOAc in pentane) to give N-(5-aminopyridin-3-yl)-2-phenylacetamide (450 mg, yield: 61%) as a light yellow solid.
N-(5-aminopyridin-3-yl)-3-phenylpropanamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
59%
With pyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; at 50℃; for 2.0h;
A mixture of 3-phenylpropanoic acid (413 mg, 2.75 mmol), pyridine-3, 5-diamine (300 mg, 2.75 mmol) and EDCI.HC1 (580 mg, 3.03 mmol) in pyridine (5 mL) was heated at 50 C for 2 h. A black solution was formed. The mixture was concentrated and the residue was poured into water (20 mL) and stirred for 2 minutes. The aqueous layer was extracted with ethyl acetate (20 mL x3). The combined organic layer was washed with water (20 mL x2) and brine (20 mL x2), dried over anhydrous Na2S04, filtered and concentrated. The residue was purified by Combi Flash (50% to 100% EtOAc in pentane) to give N-(5-aminopyridin-3- yl)-3-phenylpropanamide (400 mg, yield: 59%) as a light yellow solid. (1398) NMR (400 MHz DMSO-rie) d 2.63 (2H, t , J= 7.7 Hz), 2.91 (2H, t , J= 7.7 Hz), 5.34 (2H, brs), 7.15-7.22 (1H, m), 7.23-7.32 (4H, m), 7.38 (1H, t, J= 2.3 Hz), 7.63 (1H, d, J= 2.5 Hz), 7.86 (1H, d, .7= 2.0 Hz), 9.83 (1H, brs).
(1S,25)-N-(5-aminopyridin-3-yl)-2-phenylcyclopropane-1-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
64%
With pyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; at 50℃; for 2.0h;
A mixture of (lS,2S)-2-phenylcyclopropane-l-carboxylic acid (360 mg, 2.22 mmol), pyridine-3, 5-diamine (242 mg, 2.22 mmol) and EDCI.HC1 (468 mg, 2.44 mmol) in pyridine (5 mL) was heated at 50 C for 2 h. A black solution was formed. The mixture was concentrated and the residue was poured into water (20 mL) and stirred for 2 minutes. The aqueous layer was extracted with ethyl acetate (20 mL x3). The combined organic layer was washed with water (20 mL x2) and brine (20 mL), dried over anhydrous Na2S04, filtered and concentrated. The residue was purified by Combi Flash (50% to 100% EtOAc in pentane) to give (lS,2S)-N-(5-aminopyridin-3-yl)-2-phenylcyclopropane-l -carboxamide (390 mg, yield: 64%) as a light yellow solid. (1407) NMR (400 MHz DMSO-rie) d 1.34-1.40 (1H, m), 1.45-1.52 (1H, m), 2.05-2.11 (1H, m), 2.33-2.41 (1H, m), 5.33 (2H, brs), 7.15-7.23 (3H, m), 7.26-7.32 (2H, m), 7.34 (1H, t, .7= 2.1 Hz), 7.62 (1H, d, J= 2.5 Hz), 7.89 (1H, d, J= 2.0 Hz), 10.14 (1H, brs).
With pyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; at 50℃; for 2.0h;
A mixture of picolinic acid (338 mg, 2.75 mmol), pyridine-3, 5-diamine (300 mg, 2.75 mmol) and EDCI.HC1 (580 mg, 3.02 mmol) in pyridine (5 mL) was heated at 50 C for 2 h. A black solution was formed. LCMS (Rt = 0.329 min; MS Calcd: 214.1; MS Found: 214.9 [M+H]+). The mixture was concentrated and the residue was poured into water (20 mL) and stirred for 2 minutes. The aqueous layer was extracted with ethyl acetate (20 mL x3). The combined organic layer was washed with water (20 mL x2) and brine (20 mL x2), dried over anhydrous Na2S04, filtered and concentrated. The residue was purified by Combi Flash (50% to 100% EtOAc in pentane) to give N-(5-aminopyridin-3-yl)picolinamide (400 mg, yield: 61%) as a light yellow solid. (1416) NMR (400 MHz DMSO-rie) d 5.39 (2H, brs), 7.64 (1H, t, J= 2.3 Hz), 7.67-7.72 (2H, m),
With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 2h;
3.1 first step: 015035A1 synthesis
The compound pyridine-3,5-diamine (200mg, 1.833mmol), compound 1-Boc-azetidine-3-carboxylic acid (368.8mg, 1.833mmol), triethylamine (399.6mg, 3.666mmol) and HATU (696.5mg, 1.833mmol) was added to N,N-dimethylformamide (4mL), and the reaction was stirred at room temperature for 2 hours. The reaction solution was poured into 50ml of water, extracted with ethyl acetate, and the organic phase was washed with saturated brine. It was dried over sodium sulfate, concentrated in vacuo and purified by column chromatography to obtain a white solid compound 015035A1 (440 mg, yield 82%).
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃;
21 Example 21: Preparation of the representative compound EB2-23 of benzisoselazolone derivatives
Dissolve 2-iodobenzoic acid (5mmol) in dry dichloromethane, then add 4-dimethylaminopyridine (DMAP, 1mmol) and 3,5-pyridinediamine (5.5mmol) to the above solution, and finally Add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC·HCl, 7 mmol) and stir at room temperature overnight. The reaction solution was concentrated and purified by column chromatography to obtain N-(5-amino-3-pyridyl)-2-iodobenzamide.
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran; dichloromethane at 25℃; for 12h;
4.2.1. General procedure for synthesis of benzamide
General procedure: The syntheses of corresponding benzamide were shown in Scheme 1,2 and 3. 2-iodobenzoic acid (1 mmol, 248 mg) were dissolved in 10 mLDCM and 2.5 mL THF, then DMAP (0.2 mmol, 24.4 mg), amine (1.1mmol) and EDC (1.4 mmol, 267 mg) were added into the solution subsequently. After the mixture solution was kept stirring for 12 h at25 C. Ethyl acetate was used to extract the reaction solution. Theorganic phase was combined and dried with anhydrous magnesiumsulfate, followed by removal of the solvent by rotary evaporation, andthe crude product was purified by silica gel chromatography to obtainpurified product.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
