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Structure of 1121-60-4 * Storage: {[proInfo.prStorage]}
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With hydrogenchloride; sodium tetrahydroborate; methylamine In ethanol; dichloromethane
12-1) Preparation of 2-(methylaminomethyl)pyridine Methylamine gas was bubbled through the benzene solution(60 ml) of 10.7 g(100 mmol) of 2-pyridinecarboxaldehyde for 2 hours. Benzene was distilled off under a reduced pressure and the residue was taken up in 40 ml of ethanol. To the resulting solution was added 5.7 g of NaBH4 in three portions and the resulting mixture was stirred at room temperature for 8 hours. To the reaction mixture was added 0.5N hydrochloric acid with care not to allow the pH below 6. 300 ml of dichloromethane was added thereto and the resulting solution was washed three times with 1M NaHCO3 solution of pH 10. The organic layer was concentrated under a reduced pressure to give 10.4 g of the title compound(yield: 85percent). 1 H NMR(CDCl3) δ2.1(s, 1H), 2.5(s, 3H), 3.9(s, 2H), 7.1(t, 1H), 7.3(d, 1H), 7.6(t, 1H), 8.5(d, 1H)
85%
With hydrogenchloride; sodium tetrahydroborate; methylamine In ethanol; dichloromethane
12-1) Preparation of 2-(methylaminomethyl) pyridine Methylamine gas was bubbled through the benzene solution(60ml) of 10.7g(100mmol) of 2-pyridinecarboxaldehyde for 2 hours. Benzene was distilled off under a reduced pressure and the residue was taken up in 40ml of ethanol. To the resulting solution was added 5.7g of NaBH4 in three portions and the resulting mixture was stirred at room temperature for 8 hours. To the reaction mixture was added 0.5N hydrochloric acid with care not to allow the pH below 6. 300ml of dichloromethane was added thereto and the resulting solution was washed three times with 1M NaHCO3 solution of pH 10. The organic layer was concentrated under a reduced pressure to give 10.4g of the title compound(yield: 85percent). 1H NMR(CDCl3) δ 2.1(s, 1H), 2.5(s, 3H), 3.9(s, 2H), 7.1(t, 1H), 7.3(d, 1H), 7.6(t, 1H), 8.5(d, 1H)
Reference：
[1] Patent: US5587388, 1996, A,
[2] Patent: EP601486, 1994, A1,
[3] Magnetic Resonance in Chemistry, 1987, vol. 25, p. 696 - 706
2
[ 1121-60-4 ]
[ 74-89-5 ]
[ 21035-59-6 ]
Reference：
[1] Journal of Medicinal Chemistry, 2017, vol. 60, # 24, p. 10245 - 10256
3
[ 1121-60-4 ]
[ 593-51-1 ]
[ 21035-59-6 ]
Reference：
[1] Archiv der Pharmazie (Weinheim, Germany), 1987, vol. 320, # 7, p. 647 - 654
Reference：
[1] Chemische Berichte, 1956, vol. 89, p. 2578,2582
11
[ 1121-60-4 ]
[ 107-15-3 ]
[ 7471-05-8 ]
Reference：
[1] Tetrahedron Letters, 2005, vol. 46, # 13, p. 2197 - 2199
[2] Tetrahedron, 2007, vol. 63, # 6, p. 1474 - 1480
[3] Australian Journal of Chemistry, 2014, vol. 67, # 10, p. 1516 - 1521
[4] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 15, p. 4704 - 4708
12
[ 1121-60-4 ]
[ 7471-05-8 ]
Reference：
[1] Tetrahedron, 2007, vol. 63, # 3, p. 638 - 643
[2] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 2, p. 546 - 549
[3] Tetrahedron Letters, 2012, vol. 53, # 23, p. 2876 - 2880
13
[ 1121-60-4 ]
[ 17407-44-2 ]
Reference：
[1] Chemische Berichte, 1956, vol. 89, p. 2578,2582
14
[ 1121-60-4 ]
[ 109-04-6 ]
[ 35047-29-1 ]
Yield
Reaction Conditions
Operation in experiment
70%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.25 h; Stage #2: at -78 - 20℃; for 2.5 h; Stage #3: With water; ammonium chloride In tetrahydrofuran; hexane
Example 26Preparation of Compounds 174 and 175Step A - Synthesis of Di-(Pyridin-2-yl)-MethanolTo a -78 °C solution of 2-bromoρyridine (3.0 g, 19.0 mmol) in 60 mL THF was added w-BuLi (2.5 M in hexane, 7.6 mL, 19.0 mmol). The resulting reaction was allowed to stir at - 78 °C for about 15 minutes, then 2-pyridine carboxaldehyde (2.17 mL, 22.8 mmol) was added dropwise at -78 °C. The resulting reaction mixture was allowed to stir for 30 minutes at -78 0C, then for 2 hours at room temperature after which time the reaction was quenched with saturated aqueous NH4Cl solution. After diluting the reaction mixture with ethyl acetate, the organic layer was separated and the aqueous layer was back extracted twice with ethyl acetate. The combined organic fractions were washed with brine, dried (magnesium sulfate), filtered, and concentrated in vacuo to provide di-pyridin-2-yl-methanol in 70percent yield as a yellow oil.
Reference：
[1] Synlett, 2006, # 16, p. 2553 - 2558
[2] Synlett, 2008, # 9, p. 1418 - 1422
[3] Patent: WO2008/130581, 2008, A1, . Location in patent: Page/Page column 181
[4] Journal of Organic Chemistry, 1993, vol. 58, # 16, p. 4382 - 4388
15
[ 1121-60-4 ]
[ 35047-29-1 ]
Reference：
[1] Recueil des Travaux Chimiques des Pays-Bas, 1955, vol. 74, p. 1395,1406
Stage #1: With iodine; magnesium In tetrahydrofuran; ethylene dibromide at 20℃; for 2 h; Stage #2: at 20℃; for 2 h;
To a stirred suspension of magnesium (5.37 g, 223.75 mmol, 3 equiv) in dry THF (60 mL) under argon atmosphere was added iodine (2 crystals), 1,2-dibromo ethane (2 drops). 1-bromo-4-chlorobenzene (25.76 g, 134.39 mmol, 1.8 equiv) was then added dropwise for 1 h at room temperature. The reaction mixture was stirred at room temperature for 1 h. A solution of picolinaldehyde (8 g, 74.68 mmol) in dry THF (19 mL) was added drop wise at room temperature and stirred for 2 h. After completion of reaction, the reaction mixture was quenched with saturated ammonium chloride solution and extracted with EtOAc. The combined organic extract was washed with water, brine, dried over sodium sulfate, filteredand concentrated under reduced pressure. Purification using silica gel column chromatography (40percent EtOAc/hexanes as eluent) afforded 12.26 g of (4-chlorophenyl) (pyridin-2-yl) methanol (yield = 75percent). ESI + MS: m/z 220 ([M + Hj).
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 12, p. 3044 - 3047
[2] Journal of Medicinal Chemistry, 2007, vol. 50, # 2, p. 219 - 232
[3] Patent: WO2016/100823, 2016, A1, . Location in patent: Page/Page column 115; 116
[4] Patent: US2006/100243, 2006, A1, . Location in patent: Page/Page column 7; sheet 1
General procedure: To a solution of 2-(2’-pyridyl)-1,3-oxazoline (1, 37 mg, 0.25 mmol) and pyridine (80 L, 1.0 mmol) in H2O (6 mL), was added pyridinium hydrobromide perbromide (320 mg, 1.0 mmol) at room temperature. After stirring for 23 h at rt, the reaction mixture was treated with 0.5 M aq Na2S2O3 (10 mL), 1.0 M NaHCO3 (15 mL) and extracted with EtOAc (60 mL). The organic layer was washed with 0.5 M aq Na2S2O3 and successively washed with saturated aq NaCl, and dried over MgSO4. After removal ofsolvent in vacuo, the residue was purified by column chromatography on silica gel (Wako C-200) with CCl4, CCl4-CHCl3 (2:1 v/v). Cyanomethyl 2-pyridinecarboxylate (2, 38 mg, 0.23 mmol) was obtained in 92percent yield.
Reference：
[1] ChemMedChem, 2013, vol. 8, # 7, p. 1210 - 1223
[2] Angewandte Chemie - International Edition, 2016, vol. 55, # 12, p. 3997 - 4001[3] Angew. Chem., 2016, vol. 128, # 12, p. 4065 - 4069,5
[4] Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 20, p. 5290 - 5302
[5] Patent: WO2018/64119, 2018, A1,
29
[ 1121-60-4 ]
[ 131543-46-9 ]
[ 18653-75-3 ]
Yield
Reaction Conditions
Operation in experiment
41%
With ammonium hydroxide In ethanol; water at 0 - 20℃; for 6 h;
General procedure: An ice-cold solution of the appropriate aldehyde(2-pyridinecarboxyaldehyde (4.668 mmol) or 2-quinolinecarboxyaldehyde(3.181 mmol) in 5 mL ethanol was added to an ice cold solution of 40percent aqueous glyoxal (0.2 mL) in 5 mL ethanol,and then ice-cold concentrated aqueous NH4OH solution(0.15 mL) was added immediately. This solution was stirred at 0 C for 1 h, warmed to room temperature, and stirred for an additional 5 h. The solvent was removed under reduced pressure, andthe resulting solution was extracted several times with diethyl ether. The combined organic extracts were evaporated under reduced pressure and crystalline solids were obtained upon recrystallization with diethyl ether.
34%
With ammonium hydroxide In ethanol; water at 0 - 20℃; for 13 h; Inert atmosphere
Anhydrous ethanol (25ml), Glyoxal solution (5ml) were stirred in an ice bath, Then, picolinaldehyde (0.54g, 5.02mmol) and concentrated ammonia were added to the mixed solution under nitrogen for 1h. The mixed solution was cooled to room temperature and allowed to stand for 12h, extracted with dichloromethane and washed by water until neutral, and evaporated under reduced pressure to remove the solvent. The product was isolated using silica gel column chromatography with EtAc as the solvent. Recrystallization of the residue from EtOH afforded a brown compound (0.25g, 1.72mmol, 34percent yield).1H NMR (400MHz, DMSO) δ 12.80 (s, 1H), 8.59 (d, J=4.3Hz, 1H), 8.04 (d, J=7.9Hz, 1H), 7.88 (t, J=7.7Hz, 1H), 7.39–7.31 (m, 1H), 7.15 (s, 2H).
32%
Stage #1: at 0℃; for 0.5 h; Stage #2: With ammonia In ethanol at 0℃; for 4 h;
The overall route for synthesis is depicted by Scheme 1. The ligand was synthesized by some modification of Radziszewski method [20]. In a typical procedure, 5.0g freshly distilled pyridine-2-carboxaldehyde in 5.0ml EtOH at 0°C was added dropwise into 6.75ml glyoxal (dissolved in 5.0ml EtOH) of 0°C and was stirred for 30.0min 19.2ml ammonia at 0°C was added very slowly with constant stirring at 0°C for 4.0h. The mixture was stirred further for 18.0h at room temperature to achieve a deep brown solution. The volume of the content was then reduced to 30percent by rotary evaporator. The remaining content was extracted by diethyl ether (10times×30ml). The ether from the extracted was removed by rotary evaporator and a red oily product was found. It was distilled at 132.0°C under low pressure. Pale yellow needle like crystals were found. Yield 32percent, melting point 136.0°C. 1H NMR (500MHz, CDCl3): 8.46 (d, J=4.8, 1H), 8.09 (d, J=7.6, 1H); 7.71 (td, J=7.6, 3.8 1H); 7.68 (s, 1H), 7.18 (q, 1H), 7.13 (s, 1H). UV/Vis (MeOH): 273 (11,900), 294 (15,600). IR (KBr): ca. 3352w, 1614s, 1595s, 1508m, 1481s, 1458s, 1414s, 1379m, 1307s, 1280m, 1252m, 1171m, 1150s, 1136s, 1107m, 991s, 955s, 901m, 789s, 758s, 737s, 708m, 621s, 657m, 499m, 462m, 430w.
Reference：
[1] Journal of Fluorine Chemistry, 2011, vol. 132, # 9, p. 612 - 616
[2] Organic and Biomolecular Chemistry, 2007, vol. 5, # 4, p. 671 - 678
[3] Inorganica Chimica Acta, 2017, vol. 460, p. 63 - 68
[4] Inorganica Chimica Acta, 2019, vol. 484, p. 237 - 244
[5] Journal of Organometallic Chemistry, 2016, vol. 808, p. 42 - 47
[6] Helvetica Chimica Acta, 2005, vol. 88, # 3, p. 487 - 495
[7] Inorganic Chemistry, 2013, vol. 52, # 15, p. 8579 - 8590
[8] Patent: WO2009/11787, 2009, A1, . Location in patent: Page/Page column 102
[9] Patent: US2010/29655, 2010, A1, . Location in patent: Page/Page column 83
[10] Green Chemistry, 2011, vol. 13, # 8, p. 2100 - 2106
[11] RSC Advances, 2013, vol. 3, # 46, p. 24146 - 24153
[12] Journal of Organometallic Chemistry, 2014, vol. 751, p. 430 - 437
[13] Journal of Molecular Structure, 2017, vol. 1145, p. 102 - 111
[14] Russian Journal of General Chemistry, 2017, vol. 87, # 12, p. 2915 - 2921[15] Zh. Obshch. Khim., 2017, vol. 87, # 12, p. 2915 - 2921,7
30
[ 1121-60-4 ]
[ 107-15-3 ]
[ 18653-75-3 ]
Reference：
[1] New Journal of Chemistry, 2018, vol. 42, # 15, p. 12649 - 12665
31
[ 1121-60-4 ]
[ 1336-21-6 ]
[ 131543-46-9 ]
[ 18653-75-3 ]
Reference：
[1] Patent: US2003/96997, 2003, A1,
32
[ 1121-60-4 ]
[ 18653-75-3 ]
Reference：
[1] Chemical Communications, 2017, vol. 53, # 3, p. 651 - 654
33
[ 1121-60-4 ]
[ 90965-06-3 ]
[ 1945-84-2 ]
Yield
Reaction Conditions
Operation in experiment
71%
With potassium carbonate In methanol at 20℃; for 1.5 h;
Example 104-Methyl-2-[(E)-2-(3-methyl-5-pyridin-2-yl-3H-[1,2,3]triazol-4-yl)-vinyl]-thiazole-5-carboxylic acid isopropylamide a) 2-Ethynyl-pyridine; To a mixture of 2-pyridinecarbaldehyde (0.96 mL, 10 mmol) in MeOH (43 mL) was added potassium carbonate (2.76 g, 20 mmol) followed by a solution of (1-diazo-2-oxo-propyl)-phosphonic acid dimethyl ester (2.14 g, 11 mmol) in MeOH (14 mL) at room temperature and the resulting mixture stirred for 1.5 h. The mixture was then poured into sodium carbonate solution (1 M) and extracted with ethyl acetate and the combined organic extracts washed with brine, dried over sodium sulphate, filtered and evaporated. Purification by chromatography (silica, diethylether) afforded the title compound (728 mg, 71percent) as a yellow liquid. MS: m/e=103.0 [M]+.
71%
With potassium carbonate In methanol at 20℃; for 1.5 h;
To a mixture of 2-pyridinecarbaldehyde (0.96 mL, 10 mmol) in MeOH (43 mL) was added potassium carbonate (2.76 g, 20 mmol) followed by a solution of (l-diazo-2-oxo-propyl)- phosphonic acid dimethyl ester (2.14 g, 11 mmol) in MeOH (14 mL) at room temperature and the resulting mixture stirred for 1.5 h. The mixture was then poured into sodium carbonate solution (1 M) and extracted with ethyl acetate and the combined organic extracts washed with brine, dried over sodium sulphate, filtered and evaporated. Purification by chromatography (silica, diethylether) afforded the title compound (728 mg, 71percent) as a yellow liquid. MS: m/e = 103.0 [M]+.
Reference：
[1] Journal of the Chemical Society - Perkin Transactions 1, 1997, # 5, p. 709 - 714
[2] Journal of the Chemical Society - Perkin Transactions 1, 1997, # 5, p. 709 - 714
Reference：
[1] Journal of the American Chemical Society, 1957, vol. 79, p. 481,483
[2] Journal of Enzyme Inhibition and Medicinal Chemistry, 2016, vol. 31, # 6, p. 1069 - 1078
With copper(II) acetate monohydrate In ethanol; water at 100℃; for 2 h;
To a mixture of 3,4-diaminobenzoic acid (0.6 g, 3.94 mmol, 1 equiv) in EtOH (6 mL) andsolution of cooper acetate monohydrate (0.86 g, 4.33 mmol, 1.1 equiv) in water (10 mL),2-pyridine carboxaldehyde (0.42 mL, 4.33 mmol, 1.1 equiv) was added. The resultingmixture was stirred for 2h at 100°C. Black precipitate was filtered off and dispersed inEtOH (4 mL). Then, Na2SxH2O (1 .7 g) was added and the mixture was stirred for 30mmat 100°C. The obtained solid was filtered off from hot solution and washed with hot wateron the filter. The filtrate was acidified with HOI (pH2) and then the resulted mixture washeating at 80°C till the removing of H25. The cooled mixture was filtered off, concentratedand recrystallized from EtOH. The obtained dihydrochloride product was mixed with an equivalent quantity of KOH in ethanol. The solid was filtered off and the filtrate was concentrated to give (8) (0.447 g, 47percent) as a brown solid
Reference：
[1] Chemistry - A European Journal, 2018, vol. 24, # 13, p. 3289 - 3298
[2] Patent: WO2018/50771, 2018, A1, . Location in patent: Page/Page column 25; 26
39
[ 1121-60-4 ]
[ 1260765-26-1 ]
Reference：
[1] Journal of Heterocyclic Chemistry, 2013, vol. 50, # 6, p. 1410 - 1414
Example 26Preparation of Compounds 174 and 175Step A - Synthesis of Di-(Pyridin-2-yl)-MethanolTo a -78 C solution of 2-bromorhoyridine (3.0 g, 19.0 mmol) in 60 mL THF was added w-BuLi (2.5 M in hexane, 7.6 mL, 19.0 mmol). The resulting reaction was allowed to stir at - 78 C for about 15 minutes, then 2-pyridine carboxaldehyde (2.17 mL, 22.8 mmol) was added dropwise at -78 C. The resulting reaction mixture was allowed to stir for 30 minutes at -78 0C, then for 2 hours at room temperature after which time the reaction was quenched with saturated aqueous NH4Cl solution. After diluting the reaction mixture with ethyl acetate, the organic layer was separated and the aqueous layer was back extracted twice with ethyl acetate. The combined organic fractions were washed with brine, dried (magnesium sulfate), filtered, and concentrated in vacuo to provide di-pyridin-2-yl-methanol in 70% yield as a yellow oil.
General procedure: Appropriate aldehyde (10.5 mmol) was added to the solution of <strong>[603-81-6]2,3-<strong>[603-81-6]diaminobenzoic acid</strong></strong> 6 (1.52 g, 10 mmol) in DMF (15 mL). The solution was heated to 80 C and then stirred for about 120 h. Then, the solution was cooled to room temperature. The precipitates were filtered, washed with ethanol and dried.
With p-benzoquinone; In 1,4-dioxane; at 80℃;
General procedure: Appropriate aldehyde 3 (1.5 mmol) was added to the solution of 2,3/3,4-<strong>[603-81-6]diaminobenzoic acid</strong> 2 (1.0 mmol) in dioxane (10 mL). 1,4-Benzoquinone was added and the solution was heated to 80 C and stirred for about 6-9 h.Then, the solution was cooled to room temperature. The separated solid crystals were filtered, washed with ethanol and ether, dried. The products were used in the next step without further purification.
With potassium hydroxide; mesitylenesulfonylhydroxylamine;
EXAMPLE 88 7-Bromo-2-pyridin-2-yl-[1,2,4]triazolo[1,5-a]pyridin-5-ylamine The title compound, MS m/e (%): 290 (M+, 100), was prepared in accordance with the general method of example 63 from <strong>[329974-09-6]4-bromo-pyridine-2,6-diamine</strong>, O-mesitylene-sulfonylhydroxylamine, and pyridine-2-carbaldehyde. The purification was performed with reversed phase HPLC eluting with an acetonitrile/water gradient.
To a stirred suspension of magnesium (5.37 g, 223.75 mmol, 3 equiv) in dry THF (60 mL) under argon atmosphere was added iodine (2 crystals), 1,2-dibromo ethane (2 drops). 1-bromo-4-chlorobenzene (25.76 g, 134.39 mmol, 1.8 equiv) was then added dropwise for 1 h at room temperature. The reaction mixture was stirred at room temperature for 1 h. A solution of picolinaldehyde (8 g, 74.68 mmol) in dry THF (19 mL) was added drop wise at room temperature and stirred for 2 h. After completion of reaction, the reaction mixture was quenched with saturated ammonium chloride solution and extracted with EtOAc. The combined organic extract was washed with water, brine, dried over sodium sulfate, filteredand concentrated under reduced pressure. Purification using silica gel column chromatography (40percent EtOAc/hexanes as eluent) afforded 12.26 g of (4-chlorophenyl) (pyridin-2-yl) methanol (yield = 75percent). ESI + MS: m/z 220 ([M + Hj).
The compounds of the present invention were synthesized according to the procedure, which is illustrated schematically in FIG. 1 for three MPH alkyl analogs. Referring to FIG. 1, para-bromochlorobenzene 1 was converted into a Grignard reagent with Mg/THF which was then reacted with the pyridine-2-carboxaldehyde 2 to produce the alcohol 3. The alcohol 3 was oxidized with pyridinium chlorochromate in CH2Cl2 to produce the ketone 4. The ketone 4 was then reacted with a Grignard reagent that contains the required R group to produce the alcohol 5. After dehydration with refluxing HCl, the resulting Z and E olefin mixture 6 was hydrogenated with 10percent Pt/C in HOAc containing 3percent CF3COOH to produce the final compounds 7 with a ratio of about 40:60 of the R,R/S,S and R,S/S,R racemates for the ethyl compound. The racemates were separated by column chromatography and their relative configurations were determined by x-ray crystallography.
170 g
Into a 3 lit RB Flask, 22.28 gm of Magnesium turnings was added. 200 ml of Tetrahydrofuran and 400 ml of Toluene were added which was then heated to 65°C and reaction was initiated and added 214.4 gm of 4-Bromochlorobenzene solution in 440 ml of Toluene. After careful addition and maintenance of reaction at 75-90°C for 1 hr 30 min, cooled the contents of the reaction to 45°C. A solution of 100 gm of Pyridine-2-carbaldehyde dissolved in 200 ml Toluene was added at 48-52°C and maintained the reaction mass for 1 hr at 45-55°C, the reaction was decomposed by the addition of above reaction mass to 1 lit of 33percent Ammonium chloride solution, followed by extraction with Toluene. The Toluene layer was distilled under vacuum and the product was isolated by Hexane. Yield: 160-170 gm
With triethylamine; In ethanol; at 20 - 40℃; for 16h;
To a stirred solution of <strong>[3458-98-8]2-(3-hydroxyphenyl)ethylamine hydrochloride</strong> (4.0 g, 23.1 mmol) in ethanol (50 mL) under argon at room temperature was added Et3N (23.2 g, 231 mmol) followed by pyridine-2-carboxaldehyde (2.47 g, 23.1 mmol) and the solution was stirred at 40 C. for 16 h. The mixture was concentrated to dryness and the residue was purified by column chromatography on silica gel (CH2Cl2/MeOH/NH4OH; 90:10:1) to afford the crude product The crude was re-purified by chromatography on silica gel (CH2Cl2/MeOH/NH4OH; 95:5:0.5) to afford the desired product (580 mg, 11%) as a pale yellow solid. 1H NMR (CDCl3) 2.59 (dt, 1H, J=16.5, 4.2 Hz), 2.75-2.89 (m, 1H), 2.94-3.06 (m, 1H), 3.20 (dt, 1H, J=12.4, 5.0 Hz), 5.16 (s, 1H), 6.11 (d, 1H, J=1.9 Hz), 6.60-6.52 (m, 2H), 7.24-7.32 (m, 2H), 7.66-7.74 (m, 1H), 8.06 (d, 1H, J=4.7 Hz).
<strong>[298181-83-6]8-amino-5,6,7,8-tetrahydroquinoline</strong> (0.169 g, 1.14 mmol) was condensed with pyridine-2-carboxaldehyde (0.12 mL, 1.26 mmol) in methanol (6 mL) overnight. Hydrogenation (30 psi, room temperature) of the resulting imine over palladium on activated carbon, (10percent, 18 mg) for 6 hours provided 0.232 g of a brown oil. The oil was dissolved in CH3CN (20 mL), treated with N-[1-methylene-4-chloromethylenephenylene]-N-(diethylphosphoryl)-2-(aminomethyl)pyridine (0.38 g, 0.99 mmol) and K2CO3 (0.358 g, 2.59 mmol) and heated to reflux for 24 hours. The mixture was cooled to room temperature, concentrated, and partitioned between CH2Cl2 (40 mL) and water (20 mL). The phases were separated and the aqueous phase was extracted with CH2Cl2 (3.x.20 mL). The combined organic extracts were dried (Na2SO4) and concentrated. Purification of the crude material by column chromatography on basic alumina (20:1 CH2Cl2-CH3OH) provided 0.440 g of a yellow oil.
Example 18 1-(2-pyridyl)-1,4-pentanedione To a solution of picolinaldehyde (1.5 g) in ethanol (30 ml) were added methyl vinyl ketone (1.17 ml), 3-benzyl-5- (2-hydroxyethyl)-4-methylthiazolium chloride (378 mg) and triethylamine (0.782 ml) at room temperature, and the mixture was stirred for 12 hr. The reaction mixture was poured into 5percent aqueous potassium hydrogensulfate solution, and the aqueous layer was washed with chloroform. The aqueous layer was adjusted to pH 8 with sodium hydrogencarbonate and extracted with chloroform. The organic layer was washed with saturated brine, dried over sodium sulfate, concentrated and purified by silica gel column chromatography to give the title compound (329 mg).
A mixture of <strong>[59434-19-4]4-aminoisobenzofuran-1(3H)-one</strong> (149 mg, 1 mmol) and nicotinaldehyde (268 mg, 2.5 mmol) in ethyl propionate (10 mL) was cooled to 0 C. A solution of sodium methoxide in methanol [sodium (93 mg, 4 mmol) in methanol (3 mL)] was then added dropwise. After the addition, the mixture was stirred at 25 C. for 16 hr. The mixture was quenched with water (5 mL) and solvent was removed in vacuum. The residue was dissolved in water, and then extracted with ethyl acetate (50 mL×3). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, and concentrated to give crude product. The crude product was purified by prep-HPLC to give methyl 4-oxo-2,3-di(pyridin-2-yl)-1,2,3,4-tetrahydroquinoline-5-carboxylate (72 mg, yield 20%) and ethyl 4-oxo-2,3-di(pyridin-2-yl)-1,2,3,4-tetrahydroquinoline-5-carboxylate (14 mg, yield 3%) as a light yellow solid. LC-MS (ESI) m/z: 360(M+1)+ (methyl 4-oxo-2,3-di(pyridin-2-yl)-1,2,3,4-tetrahydroquinoline-5-carboxylate); 374(M+1)+(ethyl 4-oxo-2,3-di(pyridin-2-yl)-1,2,3,4-tetrahydroquinoline-5-carboxylate)
With magnesium sulfate; In dichloromethane;Reflux;
4-Aminoisobenzofuran-1(3H)-one (600 mg, 4 mmol), picolinaldehyde (856 mg, 8 mmol) and 1 g of MgSO4 were added into 40 mL of dichloromethane and the mixture was stirred under reflux overnight, then the mixture was evaporated under reduced pressure and the residues was dried in vacuum. 476 mg of (E)-4-(pyridin-2-ylmethyleneamino) isobenzofuran-1(3H)-one was obtained. A mixture of (E)-4-(pyridin-2-ylmethyleneamino) isobenzofuran-1(3H)-one (476 mg, 2 mmol), benzaldehyde (212 mg, 2 mmol), sodium methanolate (432 mg, 8 mmol) and ethyl propionate (40 mL) was stirred at room temperature overnight. Then the resulting mixture was evaporated under reduced pressure and extracted with ethyl acetate (100 mL×4) and concentrated. The crude product was purified by column chromatography (silica gel, petroleum ether:ethyl acetate 20:1 to 5:1) to give 30 mg of methyl 4-oxo-3-phenyl-2-(pyridin-2-yl)-1,2,3,4-tetrahydroquinoline-5-carboxylate; yield 5%. LC-MS (ESI) m/z: 459 (M+1)+.
With magnesium sulfate; In dichloromethane;Reflux;
Example 84AMethyl 4-oxo-3-phenyl-2-(pyridin-2-yl)- 1 ,2,3,4-tetrahydroquinoline-5-carboxylate[00646] 4-Aminoisobenzofuran- l(3H)-one (600 mg, 4 mmol), picolinaldehyde (856 mg, 8 mmol) and 1 g of MgSC were added into 40 mL of dichloromethane and the mixture was stirred under reflux overnight, then the mixture was evaporated under reduced pressure and the residues was dried in vacuum. 476 mg of (is)-4-(pyridin-2-ylmethyleneamino) isobenzofuran-l(3H)-one was obtained. A mixture of (£)-4-(pyridm- 2-ylmethyleneamino) isobenzofuran-l(3H)-one (476mg, 2 mmol), benzaldehyde (212 mg, 2 mmol), sodium methanolate (432 mg, 8 mmol) and ethyl propionate (40 mL) was stirred at room temperature overnight. Then the resulting mixture was evaporated under reduced pressure and extracted with ethyl acetate (100 mL x 4) and concentrated. The crude product was purified by column chromatography (silica gel, petroleum ether: ethyl acetate 20: 1 to 5: 1) to give 30 mg of methyl 4-oxo-3-phenyl-2-(pyridin-2-yl)- l,2,3,4-tetrahydroquinoline-5-carboxylate; yield 5%. LC-MS (ESI) m/z: 459 (M+l)+.
With 1,4-diaza-bicyclo[2.2.2]octane; In 1,4-dioxane; at 20℃;
General procedure: To a solution of piplartine (0.157 mmol) and aldehyde (0.189 mmol) in 1,4-dioxane (2 mL) 2 eq of DABCO was added at room temperature and the reaction allowed to stir for 72 h. Progress of the reaction was monitored by TLC. Upon completion, the reaction mixture was partitioned with tert-butyl methyl ether (5 mL) and water (3 mL). The organic phase was washed with brine (2 × 3 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by flash column chromatography on silica gel, (60-120 mesh) using hexane/EtOAc (6:4) as eluent to give the desired product
A 25 ml Teflon-lined autoclave containing 6-amino-2-naphthnoic acid (370 mg, 2 mmol), 2-pyridinecarboxaldehyde (210 mg, 2 mmol), and methanol (20 ml) was sealed and heated at 75 °C for 12 h, and then air-cooled slowly for 24 h. The resulting yellow crystals were filtered, and washed with methanol (10 ml × 3) to give ligand (67percent yield). Anal. Calc. for C17H12N2O2: C, 73.90; H, 4.38; N, 10.14. Found: C 74.00; H 4.30; N 10.15percent.
6-fluoro-2-[2-((pyridin-2-yl)methylene)hydrazino]benzothiazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
69%
With acetic acid; In ethanol; at 80℃; for 0.166667h;Microwave irradiation;
General procedure: 2-(2-Arylidenehydrazino)-6-fluorobenzothiazoles 6a-r. General Procedure D. A mixture of compound 2 (0.0549 g, 0.0003 mol), the appropriate aromatic aldehyde (0.00033 mol) and glacial acetic acid (0.1 mL) in ethanol (5 mL) was heated under microwave (20 W) at 80 °C for 10 min. On cooling, the precipitated solid was collected by filtration, washed with water, dried and crystallized from the appropriate solvent to give the desired compounds 6a-r.
diphenyl (benzo[d]thiazol-5-ylamino)(pyridin-2-yl)methylphosphonate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
95%
With hydrogen trititanate; In neat (no solvent); at 20℃; for 0.25h;Green chemistry;
General procedure: Dialkyl/diaryl phosphite (1.0 mmol) was added portion wise over a period of 5 min to the stirred mixture of heterocyclic aldehyde (1.0 mmol) and benzothiazole amine (1.0 mmol) at room temperature. Further 5 mol percent of TNT was added to the reaction mixture and the stirring was continued for 15 min. After the completion of the reaction as monitored through TLC, the reaction mixture was dissolved in EtOAc (2 mL) and the catalyst was separated by centrifugation followed by subsequent washings with EtOAc. The recovered catalyst was reused for the next cycle. The filtrate was washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated on a rotary evaporator and the resulting residue was purified by silica gel column chromatography (70:30, hexane/EtOAc) to afford the corresponding pure alpha-aminophosphonate. The novel alpha-aminophosphonates were structurally assigned by their IR, NMR (1H, 13C & 31P), and mass spectral (HRMS) analyses.
The ligand 2-(2-pyridyl)-1H-imidazo[4,5-f][1,10]phenanthroline( pipH) was prepared by the following procedure. The mixture of 2-pyridinecarboxaldehyde (160.5mg, 1.5mmol) and dap (315.1mg, 1.5mmol) in ethanol (20mL) was refluxed for 18h and then the mixture was cooled to room temperature. After filtration, the yellowish-brown precipitate was washed by cold ethanol and dried in vacuo. Yield: 61.2percent (272.6mg). 1H NMR (400MHz, DMSO-d6, delta, ppm) (see Fig. S1): 14.40 (s, 1H, NH), 9.23 (dd, J=8.2Hz, J?=1.8Hz, 1H), 9.05 (ddd, J=4.4Hz, J?=3.0Hz, J?=1.8Hz, 2H), 8.95 (dd, J=8.0Hz, J?=2.0Hz, 1H), 8.80 (ddd, J=4.8Hz, J?=1.6Hz, J?=0.9Hz, 1H), 8.44 (d, J=8.0Hz, 1H), 8.07 (td, J=8.0Hz, J?=1.8Hz, 1H), 7.84 (ddd, J=8.2Hz, J?=4.2Hz, J?=2.4Hz, 2H), 7.57 (ddd, J=7.4Hz, J?=4.8Hz, J?=1.2Hz, 1H).
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