* 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 American Chemical Society, 1947, vol. 69, p. 63,66
[2] Journal of Heterocyclic Chemistry, 1996, vol. 33, # 6, p. 1815 - 1821
[3] Journal of the American Chemical Society, 1947, vol. 69, p. 63,66
[4] Journal of Heterocyclic Chemistry, 1996, vol. 33, # 6, p. 1815 - 1821
2
[ 21901-29-1 ]
[ 56057-19-3 ]
Reference：
[1] Journal of the American Chemical Society, 1952, vol. 74, p. 3828,3830
[2] Patent: EP2366691, 2011, A1,
3
[ 1824-81-3 ]
[ 21901-29-1 ]
Yield
Reaction Conditions
Operation in experiment
29%
Stage #1: at 0℃; for 12 h; Stage #2: Cooling with ice
Example 7: Synthesis of the 6-(1-ethyleneimine)-2-carbamoyl-3-nitropyridine (compound V) [Show Image] The reagents used was ( i ) HNO3/H2SO4; (ii) NaNO2; (iii) POCl3; (iv) Na2Cr2O7; (v) SOCl2, followed by NH4OH; (vi) aziridine.Synthesis of the compound 24 A concentrated sulphuric acid (100 mL) was cooled in an ice bath, the starting material compound 23 (30 g, 0.28 mol) was slowly added and cooled to 0°C, 42 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, and the reaction was run at 0°C for 1h and left standing for 12 h. The reaction liquid was poured into 2 L of ice-water mixture, adjusted to pH=7 by adding strong aqua, and filtered. The filter cake was dried, yielding 54 g of the crude product. The above mixture was subject to wet distillation, resulting in a bright yellow liquid, and it was extracted with ethyl acetate and recrystallized in ethanol to obtain 12.5 g of the compound 24 with a melting point of 156.5-158.5°C (ethyl acetate) and a yield of 29percent.
22%
Stage #1: at -15 - 20℃; for 2 h; Stage #2: With sodium hydroxide In water
25.0 g (231 mmol) of 2-amino-6-picoline was cooled to -15(C, and dissolved very carefully in concentrated sulfuric acid (100 ml). This solution was cooled to 0(C, and 22.0 ml (60 percent, d = 1.42, 347 mmol) of nitric acid was added dropwise thereto. After the addition, the ice-water bath was removed, and after the heat generation was stopped, the reaction mixture was stirred at room temperature for 2 hours. Thereactionmixture was poured into ice (400 g), and the mixture was controlled to have pH of from 4 to 5 with aqueous 4 N sodium hydroxide solution added thereto. The precipitate formed was taken out through filtration, and washed with hot water. This was dried, and applied to a silica gel column chromatography. From the eluate with chloroform/methanol (50/1, v/v), 7.60 g (22 percent) of the entitled compound was obtained as a yellow solid.1H-NMR(DMSO-d6)δ: 2.37(3H, s), 6.61(1H, d, J=8.7Hz), 7.86(2H, brs), 8.24(1H, d, J=8.7Hz).
Reference：
[1] Journal of Medicinal Chemistry, 1996, vol. 39, # 6, p. 1331 - 1338
[2] Patent: EP2366691, 2011, A1, . Location in patent: Page/Page column 11
[3] Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 22, p. 3171 - 3176
[4] Patent: EP1479681, 2004, A1, . Location in patent: Page 122
[5] Patent: US2002/32187, 2002, A1,
4
[ 19346-45-3 ]
[ 21901-29-1 ]
Reference：
[1] Journal of Medicinal Chemistry, 2018, vol. 61, # 8, p. 3309 - 3324
5
[ 1824-81-3 ]
[ 21901-29-1 ]
Reference：
[1] Patent: US5977101, 1999, A,
6
[ 1824-81-3 ]
[ 22280-62-2 ]
[ 21901-29-1 ]
Reference：
[1] Journal of Fluorine Chemistry, 2011, vol. 132, # 8, p. 541 - 547
[2] Archiv der Pharmazie, 1995, vol. 328, # 3, p. 247 - 255
[3] Archiv der Pharmazie, 1995, vol. 328, # 3, p. 247 - 255
[4] Yakugaku Zasshi, 1952, vol. 72, p. 434[5] Chem.Abstr., 1953, p. 6404
[6] Journal of the American Chemical Society, 1955, vol. 77, p. 3154
[7] Journal of the American Chemical Society, 1947, vol. 69, p. 63,66
[8] Journal of Molecular Structure, 2013, vol. 1043, p. 15 - 27
7
[ 2802-09-7 ]
[ 71090-35-2 ]
[ 21901-29-1 ]
Reference：
[1] Liebigs Annalen der Chemie, 1986, # 2, p. 380 - 383
8
[ 2802-09-7 ]
[ 92277-16-2 ]
[ 21901-29-1 ]
Reference：
[1] Liebigs Annalen der Chemie, 1986, # 2, p. 380 - 383
9
[ 109-06-8 ]
[ 21901-29-1 ]
Reference：
[1] Journal of the American Chemical Society, 1947, vol. 69, p. 63,66
10
[ 2802-08-6 ]
[ 71090-35-2 ]
[ 21901-29-1 ]
Reference：
[1] Journal of Heterocyclic Chemistry, 1996, vol. 33, # 6, p. 1815 - 1821
11
[ 1824-81-3 ]
[ 22280-62-2 ]
[ 25864-34-0 ]
[ 21901-29-1 ]
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 11, p. 2987 - 2991
Reference：
[1] Zhurnal Russkago Fiziko-Khimicheskago Obshchestva, 1920, vol. 50, p. 536[2] Chem. Zentralbl., 1923, vol. 94, # III, p. 1022
14
[ 21901-29-1 ]
[ 39745-40-9 ]
Reference：
[1] Journal of the American Chemical Society, 1947, vol. 69, p. 63,66
15
[ 22280-62-2 ]
[ 39745-39-6 ]
[ 21901-29-1 ]
[ 28489-45-4 ]
Reference：
[1] Patent: US6011029, 2000, A,
16
[ 1824-81-3 ]
[ 22280-62-2 ]
[ 21901-29-1 ]
Reference：
[1] Journal of Fluorine Chemistry, 2011, vol. 132, # 8, p. 541 - 547
[2] Archiv der Pharmazie, 1995, vol. 328, # 3, p. 247 - 255
[3] Archiv der Pharmazie, 1995, vol. 328, # 3, p. 247 - 255
[4] Yakugaku Zasshi, 1952, vol. 72, p. 434[5] Chem.Abstr., 1953, p. 6404
[6] Journal of the American Chemical Society, 1955, vol. 77, p. 3154
[7] Journal of the American Chemical Society, 1947, vol. 69, p. 63,66
[8] Journal of Molecular Structure, 2013, vol. 1043, p. 15 - 27
17
[ 1824-81-3 ]
[ 22280-62-2 ]
[ 25864-34-0 ]
[ 21901-29-1 ]
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 11, p. 2987 - 2991
18
[ 33986-37-7 ]
[ 7664-93-9 ]
[ 22280-62-2 ]
[ 21901-29-1 ]
Reference：
[1] Zhurnal Russkago Fiziko-Khimicheskago Obshchestva, 1920, vol. 50, p. 536[2] Chem. Zentralbl., 1923, vol. 94, # III, p. 1022
19
[ 21901-29-1 ]
[ 39745-39-6 ]
Yield
Reaction Conditions
Operation in experiment
77%
at 0℃; for 16 h;
Synthesis of the compound 25 The compound 24 (10g, 0.065 mol) was added into 100 mL of water, a concentrated sulphuric acid (12 mL) was slowly added with agitation and cooled to 0 °C in an ice bath. Sodium nitrite (6.9 g, 0.098 mol) was added in batches, reacted at 0°C for 4h, and left standing for 12 h. A large amount of yellow precipitate was precipitated, filtrated under the reduced pressure, vacuum-dried to obtain 7.7 g of a yellow product with a yield of 77percent. The melting point is 216.5-218.5°C (water).
Reference：
[1] Patent: EP2366691, 2011, A1, . Location in patent: Page/Page column 11
[2] Journal of the American Chemical Society, 1952, vol. 74, p. 3828,3830
20
[ 21901-29-1 ]
[ 39745-39-6 ]
[ 56057-19-3 ]
Reference：
[1] Journal of the American Chemical Society, 1947, vol. 69, p. 63,66
[2] Journal of Heterocyclic Chemistry, 1996, vol. 33, # 6, p. 1815 - 1821
[3] Journal of the American Chemical Society, 1947, vol. 69, p. 63,66
[4] Journal of Heterocyclic Chemistry, 1996, vol. 33, # 6, p. 1815 - 1821
211 Reference Example 211; 2,3-Diamino-6-methylpyridine (I-211)
7.50 g of 5 % palladium-carbon catalyst (water content 50 %) was added to methanol (300 ml) solution of 14.9 g (97.0 mmol) of 2-amino-6-methyl-3-nitropyridine (I-210), and the resulting mixture was stirred under atmospheric pressure of hydrogen at room temperature for 2 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure, and the resulting residue was dried to obtain 11.8 g (quantitative) of the entitled compound as an ocher solid.1H-NMR(DMSO-d6)δ: 2.11(3H, s), 4.38(2H, brs), 5.26(2H, brs), 6.18(1H, d, J=7.5Hz), 6.59(1H, d, J=7.5 Hz).
100%
With hydrogen In tetrahydrofuran; ethanol for 4.25h;
14.2
To a stirred solution of 6-methyl-3-nitro-pyridin-2-ylamine (0.27 g, 1.76 mmol) in EtOH (10 niL) and THF (10 mL) was added 10% palladium on carbon (10 mg) and the reaction was purged with hydrogen for 15 minutes and then stirred for a further 4 hours under a hydrogen atmosphere (1 atm). The hydrogen atmosphere was then removed in vacuo and the resulting mixture filtered through a pad of celite, eluting with EtOAc (5OmL). The solvent was removed under reduced pressure to yield a yellow oil. (0.22 g, 100%). 1H NMR (400 MHz, MeOH-dø: δ 2.24 (s, 3H); 6.38 (d, IH, J = 7.6 Hz); 6.85 (d, 2H, J = 7.6 Hz).
100%
With palladium 10% on activated carbon; hydrogen In methanol at 20℃;
97%
With hydrogen In methanol
95%
With hydrogen In ethyl acetate
93%
With hydrogen In ethyl acetate for 1.5h; Ambient temperature;
82.9%
With water; iron; ammonium chloride In ethanol at 80℃; for 1h;
4 6-picoline-2,3-diamine
Dissolve 2-amino-3-nitro-6-picoline 4a (3.0g, 19.6mmol) in 30mL ethanol, add reduced iron powder (5.5g, 98mmol), ammonium chloride (0.5g, 9.8mmol) And 6mL water, the temperature was raised to 80°C and reacted for 1 hour. The reaction solution was filtered with Celite, and the filtrate was concentrated under reduced pressure to obtain 6-picoline-2,3-diamine 4b (2.0 g, oily liquid) with a yield of 82.9%.
75%
With platinum on activated charcoal; hydrogen In methanol at 18 - 25℃; for 4h;
246.1 Step 1: Intermediate 1
Step 1: Intermediate 1 [00803j A mixture of 6-methyl-3-nitropyridin-2-amine (500 mg, 3.26 mmol) and Pt/C (250 mg) in MeOH (12 mL) was stirred at room temperature for 4 h under hydrogen atmosphere. The reaction mixture was filtered, and the filtrate was concentrated to afford yellow solid (300 rng, 75% yield) LCMS: 124.3 [M+1].
With palladium on activated charcoal; ethanol; hydrazine hydrate
With palladium on activated charcoal; ethanol Hydrogenation;
With hydrogen In methanol
With hydrogen In ethanol
In methanol
20.b b
b 2,3-Diamino-6-methylpyridine 2-Amino-6-methyl-3-nitropyridine (754 mg, 4.92 mmol) was suspended in MeOH, and 10% Pd/C was added. The mixture was stirred briskly at RT under H2 (balloon). After 4 h, the reaction was filtered through CELITE, and the filtrate was concentrated under vacuum to afford the title compound (677. mg, quantitative).
With hydrogen In methanol at 0℃; for 2h;
536.A
Step A: A mixture of 6-methyl-3-nitro-2-pyridinamine (3 g, 19.8 mmol) and Raney Ni (1 g) in MeOH (150 ml) was stirred in an autoclave filled with H2 (50 psi) at 0 °C for 2 hours. When TLC showed the reaction was completed, the mixture was filtered, and the filtrate was concentrated to give 6-methyl-2,3-pyridinediamine.
7 g
With palladium 10% on activated carbon; hydrogen In tetrahydrofuran; methanol for 5h;
Intermediate 7
Intermediate 7: Commercially available 2-amino-6-methyl-3-nitropyridine (12 g, 78.36 mmol) was dissolved in a mixture of dry THF/MeOH (1 :1 , 60 ml_) and hydrogenated in the presence of Pd/C (10%, 1 .2 g) under 5 bar hydrogen atmosphere for 5 h. Catalyst was filtered, solvent evaporated under reduced pressure to obtain 7 g of the title compound. HPLC-MS (Method 2): Rt = 0.77 min MS : m/z = 154(M
7 g
With palladium 10% on activated carbon; hydrogen In tetrahydrofuran; methanol for 5h;
Intermediate 7
10612] Commercially available 2-amino-6-methyl-3-nitro- pyridine (12 g, 78.36 mmol) was dissolved in a mixture of dry THF/MeOH (1:1, 60 mE) and hydrogenated in the presence of Pd/C (10%, 1.2 g) under 5 bar hydrogen atmosphere forh. Catalyst was filtered, solvent evaporated under reduced pressure to obtain 7 g of the title compound.10613] HPEC-MS (Method 2): R=0.77 mm10614] MS: mlz=154 (M+H)
With palladium 10% on activated carbon; hydrogen at 20℃; Inert atmosphere; Sealed tube;
With palladium on activated charcoal; hydrogen In ethanol; ethyl acetate for 0.333333h;
In methanol
46.b b
b 2,3-Diamino-6-methylpyridine 2-Amino-6-methyl-3-nitropyridine (754 mg, 4.92 mmol) was suspended in MeOH, and 10% Pd/C was added. The mixture was stirred briskly at RT under H2 (balloon). After 4 h, the reaction was filtered through Celite, and the filtrate was concentrated under vacuum to afford the title compound (677 mg, quantitative): 1 H NMR (250 MHz, CD3 OD) δ 6.82 (d, 1H), 6.36 (d, 1H), 2.25 (s, 3H).
With sulfuric acid; water; sodium nitrite; at 0℃; for 16h;
Synthesis of the compound 25 The compound 24 (10g, 0.065 mol) was added into 100 mL of water, a concentrated sulphuric acid (12 mL) was slowly added with agitation and cooled to 0 C in an ice bath. Sodium nitrite (6.9 g, 0.098 mol) was added in batches, reacted at 0C for 4h, and left standing for 12 h. A large amount of yellow precipitate was precipitated, filtrated under the reduced pressure, vacuum-dried to obtain 7.7 g of a yellow product with a yield of 77%. The melting point is 216.5-218.5C (water).
With acetic acid at 120℃; for 2h; Inert atmosphere;
(a) General procedure for the synthesis of 1a-1u[1]
General procedure: Compound 1a was purchased from commercial sources and used as received. Substituted 2-(1H-pyrrol-1-yl)anilines 1b-1u were prepared in the following method. A mixture of substituted S1 (5 mmol) and S2 (5 mmol) in acetic acid (25 mL) wasrefluxed for 2 h with vigorous stirring. After cooling, the reaction mixture was poured into water (100 mL) and extracted with ethyl acetate three times (3×20 mL). The combined organic layers were dried with anhydrous Na2SO4 and the solvent was removed in vacuo to afford S3. Then, the residue S3 was added to iron powder (20 mmol)and NH4Cl (2 mmol) in water (20 mL) and refluxed for 4 h. After cooling, the reaction mixture was poured into water (100 mL) and extracted with ethyl acetate three times (3×20 mL). The combined organic layers were dried with anhydrous Na2SO4 and the solvent was removed in vacuo to afford a residue. The residue was purified by column chromatography on silica gel using petroleum ether/EtOAc as eluent to provide the desired product 1b-1u.
With sulfuric acid; nitric acid for 2h; Ambient temperature;
29%
Stage #1: 2-Amino-6-methylpyridine With sulfuric acid; nitric acid at 0℃; for 12h;
Stage #2: In water Cooling with ice;
7
Example 7: Synthesis of the 6-(1-ethyleneimine)-2-carbamoyl-3-nitropyridine (compound V) [Show Image] The reagents used was ( i ) HNO3/H2SO4; (ii) NaNO2; (iii) POCl3; (iv) Na2Cr2O7; (v) SOCl2, followed by NH4OH; (vi) aziridine.Synthesis of the compound 24 A concentrated sulphuric acid (100 mL) was cooled in an ice bath, the starting material compound 23 (30 g, 0.28 mol) was slowly added and cooled to 0°C, 42 mL of a mixture in volumetric ratio of 1:1 of a concentrated sulphuric acid (98%) and a concentrated nitric acid (72%) was slowly added, and the reaction was run at 0°C for 1h and left standing for 12 h. The reaction liquid was poured into 2 L of ice-water mixture, adjusted to pH=7 by adding strong aqua, and filtered. The filter cake was dried, yielding 54 g of the crude product. The above mixture was subject to wet distillation, resulting in a bright yellow liquid, and it was extracted with ethyl acetate and recrystallized in ethanol to obtain 12.5 g of the compound 24 with a melting point of 156.5-158.5°C (ethyl acetate) and a yield of 29%.
26%
With sulfuric acid; nitric acid at 80℃;
22%
Stage #1: 2-Amino-6-methylpyridine With sulfuric acid; nitric acid at -15 - 20℃; for 2h;
Stage #2: With sodium hydroxide In water
210 Reference Example 210; 2-Amino-6-methyl-3-nitropyridine (I-210)
25.0 g (231 mmol) of 2-amino-6-picoline was cooled to -15(C, and dissolved very carefully in concentrated sulfuric acid (100 ml). This solution was cooled to 0(C, and 22.0 ml (60 %, d = 1.42, 347 mmol) of nitric acid was added dropwise thereto. After the addition, the ice-water bath was removed, and after the heat generation was stopped, the reaction mixture was stirred at room temperature for 2 hours. Thereactionmixture was poured into ice (400 g), and the mixture was controlled to have pH of from 4 to 5 with aqueous 4 N sodium hydroxide solution added thereto. The precipitate formed was taken out through filtration, and washed with hot water. This was dried, and applied to a silica gel column chromatography. From the eluate with chloroform/methanol (50/1, v/v), 7.60 g (22 %) of the entitled compound was obtained as a yellow solid.1H-NMR(DMSO-d6)δ: 2.37(3H, s), 6.61(1H, d, J=8.7Hz), 7.86(2H, brs), 8.24(1H, d, J=8.7Hz).
1.7%
With sodium hydroxide; Concentrated HNO3; sulfuric acid
20.a a
a 2-Amino-6-methyl-3-nitropyridine 2-Amino-6-picoline (5.1 g, 47.1 mmol) was weighed into a 500 mL round bottom flask, and the flask was cooled to -30° C. Concentrated H2SO4 (20 mL) was added, which caused some fuming to occur. Concentrated HNO3 (10 mL, 160 mmol) was then added dropwise slowly. The reaction was allowed to warm to RT over 30 min, then was heated in an oil bath set at 80° C. After 90 min, the reaction was removed from the heating bath. and ice was added. 6.25 N NaOH (150 mL, 937.5 mmol) was added slowly, and the resulting yellow precipitate was collected on a sintered glass funnel. Drying in a vacuum desiccator gave the title compound (1.7,24%).
2-amino-6-[(β-N,N-dimethylamino)vinyl]-3-nitropyridine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
55.2%
In N,N-dimethyl-formamide at 140℃; for 16h; Inert atmosphere;
41%
In N,N-dimethyl-formamide at 100℃; for 18h; Inert atmosphere;
To the solution of 6-amino-5-nitro-2-picoline (12.6 g, 80.3 mmol) in dry N,N-dimethyl25 formamide (120 mL) under argon atmosphere 25.5 g (201 mmol) of N,N-dimethylformamide(DMA) dimethyl acetal were added. The whole was heated at 110 °C for 18 hours. The mixture was concentrated to ca. of initial volume, and after addition of 60 mL of water stirred at room temperature for 16 hours. Precipitated dark-red solid was successfully washed with water and methanol and dried under reduced pressure. 6.97 g of 6-[(E)-2-(dimethylamino)-ethenyl]-3-nitropyridine-2-amine were obtained (yield 41%). MS-ESI: (mlz) calculated for C9H13N402 [M-H]: 209.10, found 209.1.
{4-methyl-7-[(5-methyl-1<i>H</i>-imidazo[4,5-<i>b</i>]pyridin-2-ylmethyl)-carbamoyl]-3-oxo-2,3,4,5-tetrahydro-1<i>H</i>-benzo[<i>e</i>][1,4]diazepin-2-yl}-acetic acid[ No CAS ]
A. 2-Hydroxy-5-nitro-6-methylpyridine To a suspension of a 2:1 mixture of 2-amino-5-nitro-6-methylpyridine and 2-amino-3-nitro-6-methylpyridine (2.5 g, 16.3 mmol) in 15 mL of water at 0 C. was added concentrated sulfuric acid (5 mL), followed by a solution of NaNO2 (2.25 g, 32.6 mmol) in 5 mL of water dropwise over 90 minutes. The solution was stirred 5 hours as it warmed to room temperature, cooled to 0 C. and filtered. The solid was washed with water (2*) and dried under vacuum to afford 1.84 g of a >4:1 mixture (by HPLC) of Compound A and <strong>[39745-39-6]2-hydroxy-3-nitro-6-methylpyridine</strong> (73%) as a tan solid.
46.a a
a 2-Amino-6-methyl-3-nitropyridine 2-Amino-6-picoline (5.1 g, 47.1 mmol) was weighed into a 500 mL round bottom flask, and the flask was cooled to -30° C. Concentrated H2 SO4 (20 mL) was added, which caused some fuiming to occur. Concentrated HNO3 (10 mL, 160 mmol) was then added dropwise slowly. The reaction was allowed to warm to RT over 30 min, then was heated in an oil bath set at 80° C. After 90 min, the reaction was removed from the heating bath, and ice was added. 6.25 N NaOH (150 mL, 937.5 mmol) was added slowly, and the resulting yellow precipitate was collected on a sintered glass funnel. Drying in a vacuum desiccator gave the title compound (1.7 g, 24%): TLC Rf (5% MeOH/CHCl3) 0.77; 1 H NMR (250 MHz, CDCl3) δ 8.31 (d, 1H), 6.32 (d, 1H), 2.46 (s, 3H); MS (ES) m/e 154.0 (M+H)+.
Step 1 Preparation of 2-amino-6-methyl-3,5-dinitropyridine To a stirred solution of 2-amino-6-methylpyridine (38 g, 352 mmol) in conc. H2 SO4 (70 mL) at 0 C. was added HNO3 (16.5 mL, d=1.49) drop-wise over 30 min. The mixture was warmed stirred an additional 1 h at 0 C. then poured into 500 g of ice. This heterogeneous mixture was stirred for 1 h at r.t., filtered, washed with 50 mL H2 O and the residue was briefly dried to give 58 g of crude moist 6-methyl-2-nitraminopyridine. This solid was carefully added in 1-2 g portions to stirred H2 SO4 (70 mL) at 40 C. After complete addition, the reaction mixture was stirred 1 h at 40 C., cooled and poured into 500 g of ice. The resulting precipitate was filtered, washed with 50 mL of H2 O, and air dried to give a yellow solid. 8.5 g of this mixture of 2-amino-6-methyl-3-nitropyridine and 2-amino-6-methyl-5-nitropyridine was dissolved in H2 SO4 (100 mL) at 0 C. and HNO3 (2.74 mL, d=1.49) was added drop-wise over 10 min. After complete addition, the mixture was warmed to 50 C. for 90 min., cooled, then poured onto 200 g of ice. The residue was collected by filtration and washed with cold H2 O (2*50 mL) to give 2-amino-6-methyl-3,5-dinitropyridine as a yellow solid.
110.A Step A
Step A Preparation of 6-methyl-3-nitro-2-pyridone A solution of 24 g. of 2-amino-6-methyl-3-nitro-pyridine in 25 ml. of concentrated sulfuric acid and 380 ml. of water was cooled to 0° C. and treated with 11 g. of sodium nitrite in 25 ml. of water. The temperature spontaneously rose to 45° C. After cooling, the precipitate of 6-methyl-3-nitro-2-pyridone was collected (m.p. 222°-223° C.) and used directly in the next step.
3-(2,6-dichloro-3,5-dimethoxyphenyl)-7-chloro-2H-pyrano[3,2-c]pyridine-2-one[ No CAS ]
[ 21901-29-1 ]
C22H16Cl2N4O6[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
46%
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos In toluene at 110℃; for 4h; Inert atmosphere;
96
A 100 mL round bottom flask was added A (200 mg, 0.517 mmol)(95 mg, 0.620 mmol), Pd2 (dba) 3 (48 mg, 0.052 mmol), X-phos (49 mg, 0.103 mmol), cesium carbonate (505 mg, 1.55 mmol), toluene (12 mL) (4: 1) in a 110 ° C oil bath for 4 h, cooled to room temperature, filtered, washed with a mixed solvent of dichloromethane and methanol (5: 1). The filtrates were combined and the solvent was evaporated. The resulting residue was purified by column chromatography Dichloromethane: methanol 100: 1) to give yellow solid C (120 mg, yield 46.0%).
ethyl 5-methyl-1-(((6-methyl-3-nitropyridin-2-yl)amino)methyl)-1H-pyrazolecarboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
52.3%
In dichloromethane at 20℃; for 96h;
2.2.1. Preparation of compounds (L1 - L3)
General procedure: The three compounds were prepared by the same procedure analogue for L1. L1 was prepared by a similar procedure asdescribed in the literature [21]. The CH2Cl2 solution (10.0 mL) ofpyrimidinamine (1.15 g, 12.09 mmol) was added to the CH2Cl2 solution(10.0 mL) of 1H-1-pyrazolyl-1-methanol (1.86 g,12.09 mmol). The reaction solution was dried over MgSO4 afterstirring at room temperature for 4 days. The filtrate solvent, underreduced pressure, produced a transparent oil andwas recrystallizedusing a mixture of methanol with a few drops of ether. The whitecrystals obtained after 3 days were filtered and washed withmethanol (2 50 mL), followed by washing with Et2O (2 50 mL)to yield the final product (L1).
Synthesis of proton transfer salts (15-20)
General procedure: A solution of 5 mmol 1 (1.271 g) in 25 mL ethanol was added to the solution of 5 mmol 2-7 (1.001 g 2 for 15;0.551 g 3 for 16; 0.541 g 4 for 17; 0.696 g 5 for 18; 0.766 g6 for 19; 0.766 g 7 for 20) in 25 mL ethanol. The mixture was refluxed for 3 h and then was cooled to room temperature. The reaction mixture was kept at room temperature for 3 h to give white solids of 15-20 (1.987 g, 95% yield for 15; 1.477 g, 90% yield for 16; 1.387 g, 85% yield for 17;1.572 g, 88% yield for 18; 1.615 g, 87% yield for 19 and1.726 g, 93% yield for 20) (Fig. 2).
Synthesis of simple metal complexes (9-14)
General procedure: A solution of 1 mmol (0.199 g) Cu(CH3COO)2*H2Oin water (10 mL) was added dropwise to the solution of1 mmol (0.200 g 2 for 9; 0.110 g 3 for 10; 0.108 g 4 for11; 0.139 g 5 for 12; 0.153 g 6 for 13; 0.153 g 7 for 14) inwater/ethanol (1:1) (20 mL) with stirring for 4 days at room temperature to give powdery solids of 9-14 (red, 0.172 g,70% yield for 9; green, 0.092 g, 65% yield for 10; blue,0.159 g, 80% yield for 11; brown, 0.111 g, 60% yield for12; orange, 0.138 g, 75% yield for 13; turquoise, 0.129 g,65% yield for 14) (Fig. 1).
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