* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Reference：
[1] Journal of the Chemical Society, 1954, p. 2693,2697
[2] Doklady Akademii Nauk SSSR, 1952, vol. 84, p. 289,292[3] Chem.Abstr., 1953, p. 3309
10
[ 109-06-8 ]
[ 18368-63-3 ]
Reference：
[1] Zhurnal Russkago Fiziko-Khimicheskago Obshchestva, 1920, vol. 50, p. 536[2] Chem. Zentralbl., 1923, vol. 94, # III, p. 1022
11
[ 931-19-1 ]
[ 10025-87-3 ]
[ 18368-63-3 ]
[ 3678-63-5 ]
[ 4377-33-7 ]
Reference：
[1] Yakugaku Zasshi, 1951, vol. 71, p. 217,218[2] Chem.Abstr., 1952, p. 4541
[3] Yakugaku Zasshi, 1955, vol. 75, p. 1233[4] Chem.Abstr., 1956, p. 8664
12
[ 931-19-1 ]
[ 10025-87-3 ]
[ 18368-63-3 ]
[ 3678-63-5 ]
[ 4377-33-7 ]
Reference：
[1] Yakugaku Zasshi, 1951, vol. 71, p. 217,218[2] Chem.Abstr., 1952, p. 4541
[3] Yakugaku Zasshi, 1955, vol. 75, p. 1233[4] Chem.Abstr., 1956, p. 8664
13
[ 18368-63-3 ]
[ 5315-25-3 ]
Reference：
[1] European Journal of Organic Chemistry, 2002, # 24, p. 4181 - 4184
Reference：
[1] Angewandte Chemie, 1992, vol. 104, # 6, p. 748 - 749
[2] Angewandte Chemie, 1992, vol. 104, # 6, p. 748 - 749
[3] Chemical and Pharmaceutical Bulletin, 1990, vol. 38, # 9, p. 2446 - 2458
[4] Journal of Organic Chemistry, 1958, vol. 23, p. 1287
[5] Patent: CH227124, 1941, ,
16
[ 18368-63-3 ]
[ 79055-63-3 ]
Reference：
[1] Patent: WO2008/112217, 2008, A1,
17
[ 18368-63-3 ]
[ 5315-24-2 ]
Yield
Reaction Conditions
Operation in experiment
49.35%
at 119℃; for 36 h;
[0719] a mixture of compound 84a (5 g, 39.19 mmol) and νη2νη2.η20 (20 g, 391.94 mmol) was heated under reflux (119 °C) for 36 hours. The reaction mixture was concentrated under reduced pressure to remove the unreacted hydrazine hydrate. The residue was diluted with H2O (30 ml) and extracted with DCM (30 ml x 3). The combined organic layers were washed with brines (30 ml), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by re-crystallization from petroleum ether (15 ml) at -10 °C to give compound 84b (2.40 g, yield: 49.35percent) as a black brown solid. 1H NMR (400mhz, DMSO-d6) δ 7.39 - 7.29 (m, 1h), 7.25 (s, 1h), 6.51 (d, j = 8.4 hz, 1h), 6.39 (d, j = 7.3 hz, 1h), 4.06 (s, 2h), 2.26 (s, 3h). MS (ESI) m/z (M+H)+ 127.8.
Reference：
[1] Patent: US2003/187014, 2003, A1,
[2] Patent: WO2018/64119, 2018, A1, . Location in patent: Paragraph 0719
[3] Patent: US4622401, 1986, A,
[4] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 6, p. 1743 - 1747
18
[ 18368-63-3 ]
[ 33674-97-4 ]
Yield
Reaction Conditions
Operation in experiment
18%
Stage #1: With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 40℃; for 1.5 h; Stage #2: at 100℃; for 1 h; Stage #3: With sodium hydroxide; water In methanol at 0℃; for 0.5 h;
Manufacturing Example 52-1-1 (6-Chloro-pyridin-2-yl)-methanol; To a mixture of 2-chloro-6-methylpyridine (1.0 g, 7.84 mmol) and dichloromethane (20 mL) was added m-chloroperbenzoic acid (3.5 g, 13.2 mmol) on an ice bath, which was stirred for 1.5 hours at 40° C. Water and sodium hydrogencarbonate were added to the reaction mixture, which was then extracted with dichloromethane. The organic layer was separated, washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure. Acetic anhydride (20 mL) was added to the resulting residue and stirred for 1 hour at 100° C. The reaction mixture was cooled to room temperature and concentrated under a reduced pressure. A 5 N aqueous sodium hydroxide solution (4 mL, 20.1 mmol) was added to a mixture of the resulting residue and methanol (20 mL) on an ice bath, which was stirred for 30 minutes. Water was added to this mixture, which was then extracted with ethyl acetate. The organic layer was separated, washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=3:1) to obtain the title compound (200.0 mg, 18percent).1H-NMR Spectrum (CDCl3) δ (ppm): 3.08 (1H, brs), 4.75 (2H, d, J=5.2 Hz), 7.23-7.27 (2H, m), 7.64-7.69 (1H, m).
Reference：
[1] European Journal of Organic Chemistry, 2002, # 24, p. 4181 - 4184
[2] European Journal of Organic Chemistry, 2002, # 24, p. 4181 - 4184
21
[ 18368-63-3 ]
[ 78846-88-5 ]
[ 78152-53-1 ]
Reference：
[1] Journal of Organic Chemistry, 2000, vol. 65, # 23, p. 7718 - 7722
22
[ 18368-63-3 ]
[ 78846-88-5 ]
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 5, p. 453 - 458
23
[ 18368-63-3 ]
[ 83782-89-2 ]
Reference：
[1] Journal of Medicinal Chemistry, 1983, vol. 26, # 2, p. 218 - 222
24
[ 18368-63-3 ]
[ 124-38-9 ]
[ 885267-14-1 ]
Reference：
[1] Tetrahedron, 1995, vol. 51, # 5, p. 1337 - 1344
[2] Journal of Organic Chemistry, 2001, vol. 66, # 20, p. 6595 - 6603
25
[ 18368-63-3 ]
[ 616-38-6 ]
[ 161807-18-7 ]
Reference：
[1] Journal of the American Chemical Society, 2010, vol. 132, # 41, p. 14391 - 14393
[2] Patent: WO2013/134562, 2013, A1, . Location in patent: Paragraph 00202
26
[ 18368-63-3 ]
[ 161807-18-7 ]
Reference：
[1] Journal of Organic Chemistry, 2001, vol. 66, # 20, p. 6595 - 6603
[2] Tetrahedron, 1995, vol. 51, # 5, p. 1337 - 1344
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -70℃; for 0.5 h; Stage #2: at -70 - 20℃; for 1.5 h; Stage #3: With water; ammonium chloride In tetrahydrofuran; hexane
Reference example 6: (-chloro-pyridin-2-yl)-acetic acid ethyl ester. n-Butyl lithium (23percent in hexane, 13.2 mL, 47.3 mmol) was added dropwise to a cold solution (-70 °C) of 2-chloro-6-methyl-pyridine (5.0 g, 39.4 mmol) in tetrahydrofuran (30 mL) and stirred for 30 min at -70 0C. Diethyl carbonate (5.75 mL, 47.3 mmol) was added slowly and the reaction mixture stirred for 30 min at -70 °C before warming to room temperature and stirring for a further Ih. The reaction mixture was quenched into saturated ammonium chloride solution and extracted with ethyl acetate. The organic layer was washed with water and brine, then dried over sodium sulfate, filtered and concentrated to yield the crude compound which was purified by column chromatography over silica gel (100-200 mesh), using 9 percent ethyl acetate in petroleum ether as eluent, to afford (6-chloro-pyridin-2-yl)-acetic acid ethyl ester (2.21 g, 28 percent) as an oil.
With trifluorormethanesulfonic acid In chlorobenzene at 130℃; for 21h; Inert atmosphere;
89.1%
Stage #1: diphenylphosphane With n-butyllithium In tetrahydrofuran; hexane at 20℃; for 1h;
Stage #2: 6-chloro-2-picoline In tetrahydrofuran; hexane at 20℃; for 2h;
77%
With n-butyllithium In tetrahydrofuran at 20℃; for 3h;
Stage #1: bis(pyridin-2-yl)methylamine With n-butyllithium In tetrahydrofuran at 20℃; for 4h;
Stage #2: 6-chloro-2-picoline In tetrahydrofuran for 18h; Heating; Further stages.;
With lithium hexamethyldisilazane In tetrahydrofuran at 45℃; for 15h;
66%
With lithium hexamethyldisilazane In tetrahydrofuran
1.a 3-(2-Anilino-4-pyrimidinyl)-N-cyclopentyl-2-(4-fluorophenyl)-pyrazolo[1,5-a]pyridin-7-amine
a) 2-(6-Chloro-2-pyridinyl)-1-(4-fluorophenyl)ethanone. To a cold (0° C.) solution of 6-chloro-2-picoline (21.4 mL, 196.0 mmol) and ethyl 4-fluorobenzoate (57.5 mL, 391.2 mmol) in tetrahydrofuran (311 mL) was added lithium bis(trimethylsilyl)amide (391 mL, 1.0 M in tetrahydrofuran, 391.0 mmol) dropwise via a pressure equalizing funnel over 1 hour. Upon complete addition, the cold bath was removed and the resultant solution was heated to 45° C. for 15 hours. The mixture was cooled to room temperature and quenched by the addition of water. Ether was added and the organic layer was washed with brine. The aqueous layer was extracted with ether and the combined organics were dried over magnesium sulfate. Filtration and concentration gave a solid residue which was purified by recrystallization from ethyl acetate-hexanes to provide 2-(6-chloro-2-pyridinyl)-1-(4-fluorophenyl)ethanone (32.2 g, 66%) as a tinted off-white solid existing as a keto-enol tautomeric mixture. 1H NMR (CDCl3): for the keto tautomer δ 8.11 (m, 2H), 7.66 (t, 1H), 7.30-7.25 (m 2H), 7.17 (t, 2H), 4.48 (s 2H), 19F NMR (CDCl3) δ -104.72 (keto), -111.64 (enol); MS m/z 250 (M+1).
6 Example 6
Example 6 2.55 g of 6-chloro-2-picoline and 1.00 g of sodium hydroxide are stirred into a mixture of 15 ml of water and 8 ml of methanol. Following the addition of 1.3 g of palladium (5% by weight on activated carbon) as catalyst, the mixture is stirred for 20 h at 80-85° C. at 0.1 MPa. The mixture is then diluted with 20 ml of methanol and the catalyst is filtered off. After the methanol has been stripped off, the product, 6,6'-dimethyl-2,2'-bipyridyl, crystallizes in the form of lamellar crystals. This gives 1.10 g (58% yield). According to 1H NMR, the crude product has a purity of >98%. CAS Registry Number: 4411-80-7. 1H NMR (300 MHz, DMSO): d=8.18 (d, J=8 Hz, 2H); 7.81 (t, J=8 Hz, 2H); 7.29 (d, J=8 Hz, 2H); 2.56 (s, 6H).
With copper(l) iodide; triethylamine; triphenylphosphine In acetonitrile at 82℃;
With zinc In 1-methyl-pyrrolidin-2-one at 20 - 70℃; Inert atmosphere;
24
To a glass reaction container equipped with a cooling apparatus, 15.3 mg of nickel bromide, 25.2 mg of 5,5'-bis(trimethylsilyl)-2,2'-bipyridine and 91.6 mg of zinc powder were added under an atmosphere of nitrogen at room temperature. To the obtained mixture, 89.3 mg of 6-chloro-2-picoline and 5 mL of N-methyl-2-pyrrolidone were added at room temperature. The obtained mixture was reacted at 70°C for 2 hours to obtain a reaction mixture containing 6,6'-diemthyl-2,2'-bipyridine. The yield of 6,6'-dimethyl-2,2'-bipyridine was 60.8 mg.
With lithium hexamethyldisilazane In tetrahydrofuran at 0 - 45℃;
86%
With lithium hexamethyldisilazane In tetrahydrofuran; methanol
5.a [3-({4-[7-(Cyclopentylamino)-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinyl}amino)phenyl](phenyl)methanone
a) 2-(6-Chloro-2-pyridinyl)-1-(4-methoxyphenyl)ethanone. To a cold (0° C.) solution of 6-chloro-2-picoline (18.3 mL, 166.5 mmol) and ethyl 4-methoxybenzoate (30.0 g, 166.5 mmol) in tetrahydrofuran (300 mL) was added lithium bis(trimethylsilyl)amide (333 mL 1.0 M in tetrahydrofuran, 332.7 mmol) dropwise via a pressure equalizing funnel over 1 hour. Upon complete addition, the cold bath was removed and the resulting solution was heated at 45° C. for 15 hours. The mixture was cooled to room temperature, and the solution was concentrated. Methanol was added to quench the reaction, resulting in the formation of a yellow precipitate. The precipitate was collected by filtration and dried to give 2-(6-chloro-2-pyridinyl)-1-(4-methoxyphenyl)ethanone (37.4 g, 86%) as a yellow solid. 1H NMR (CDCl3): δ 7.99 (d, 2H), 7.57 (t, 1H), 7.22-7.19 (m, 2H), 6.90 (d, 2H), 4.39 (s, 2H), 3.83 (s, 3H); MS m/z 262 (M+1).
(1) 2-Methoxy-6-methylpyridine 100ml of sodium methoxide (28% methanol solution) was added to 20.lg of 2-chloro-6-methylpyridine at room temperature, this reaction liquid was heated to reflux for 2 days. After standing to cool, water and ethyl acetate were added thereto, and the organic layer was separated. The resulting organic layer was washed with brine and then dried over anhydrous sodium sulfate. After removing the drying agent by filtration, the organic layer was concentrated under a reduced pressure to give 16.8g of the title compound. 1H-NMR (CDCl3) delta (ppm): 2.44(s,3H), 3.90(s,3H), 6.51(d, 1H, J=8.4Hz), 6.68(d, 1H, J=8.0Hz), 7.43(dd, 1H, J=8.4Hz,8.0Hz).
With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; for 16.0h;Reflux;
Method XXIII2-(bromomethyl)-6-chloropyridineA solution of 2-chloro-6-methylpyridine (2 g, 15.68 mmol), N-bromosuccinimide (1.462 mL, 17.25 mmol) and benzoyl peroxide (0.380 g, 1.57 mmol) in carbontetrachloride (35ml) was refluxed for 16 hr. The succinimide was removed by filtration and the solution washed with water, dried (magnesiumsulphate), filtered and evaporated to give the title compound (1.44g, 45%). m/z (APCI) (M+H)+ 207.
With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; for 72.0h;Heating / reflux;
A solution of 3-chloro-6-methyl pyridine (220 mg, 1.72 mmol) in carbontetrachloride (4 mL) was heated with NBS (284 mg, 1 .60 mmol) and benzoyl peroxide (100 mg) for 3 days. The reaction was worked up by removal of the solvent and resuspension of the production in CH2Cl2. The organic layer was washed with aqueous 2N NaOH (2 x 50 mL) and dried in vacuo to give 170 mg of the product as a clear oil; EI MS (m/z) 208.0, 210.0 [M+H]. A solution of compound IV (102 mg, 0.330 mmol) in CH2Cl2(3.0 mL) was was added DlEA (0.121 mL, 0.692 mmol) and TMSCl (0.088 mL, 0.692 mmol) at 00C. The reaction was allowed to warm up to rt and stirred for 1 hour. To the mixture was added 2-(bromomethyl)-6-chloropyridine (102 mg, 0.330 mmol) in DIEA (0.121 mL, 0.692 mmol). This reaction was stirred at rt over night when it was worked up by addition of CH2Cl2 and saturated aqueous NH4Cl. The organic layer was dried in vacuo and purified <n="194"/>using silica gel chromatography to give 140 mg (97%) of the product as a clear oil. EI MS (m/z) 457.0 [M+Na]. 'A solution benzyl (l S,2S)- l -((S)-((6-chloropyridin-2- yl)methyl)(ethoxy)phosphoryl)-2-vinylcyclopropylcarbamate (1 18 mg, 0.271 mmol) in acetonitrile (2.71 mL) was treated with TMSI (0.193 mL, 1/35 mmol) for 1 .5 hours at rt when the reaction was complete. The reaction was quenched by addition of TEA (0.377 mL, 2.71 mmol) and MeOH (10 mL) and the residue was dried and used as is; EI MS {m/z) 273.1 [MH+]. A solution of (S)-((lS,2S)-l-amino-2-vinylcyclopropyl)((6- chloropyridin-2-yl)methyl)phosphinic acid (74 mg, 0.271 mmol), carboxylic acid VII (177 mg, 0.271 mmol) in DMF (1.3 mL) was stirred with HATU (155 mg, 0.407 mmol) and DIEA (0.189 mL, 1.09 mmol) for 1 hour when the reaction was complete. The product was purified by RP HPLC (ACN, 0.05% TFA- H2O, 0.05% TFA) to provide 37 mg of the desired product. 1H NMR (300 MHz, CD3OD) 5 8.29 (d, IH, J= 9 Hz), 8.17 (s, IH), 7.77-7.65 (m, 3H), 7.43 (dd, IH, J= 2, 8 Hz), 7.35-7.27 (m, 2H), 5.92-5.75 (m, 2H), 5.23 (d, IH, J= 17 Hz), 5.01 (d, IH, J= 12 Hz), 4.75-4.61 (m, 2H), 4.50 (br s, IH), 4.20-4.08 (m, 3H), 4.05 (s, 3H), 3.53 (dd, 2H, J= 3, 17 Hz), 2.84-2.74 (m, IH), 2.65-2.53 (m, IH), 2.16-2.04 (m, IH), 1.70-1.42 (m, 10 H), 1.34 (d, 6H, J= 6 Hz), 1.03 (s, 9H); 31P (121.4 MHz, CD3OD) delta. 40.7; EI MS (m/z) 907.4 [MH+].
With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In tetrachloromethane; at 80℃; for 3.0h;Inert atmosphere;
2-Chloro-6-methylpyridine (1 10mg, Aldrich), N-bromosuccinimide (153mg) and AIBN (14.16mg) were dissolved in carbon tetrachloride (2ml) and the reaction mixture stirred at 80 0C under argon for three hours. The reaction mixture was allowed to cool to room temperature, filtered through Kieselguhr, washed with dichloromethane and evaporated to afford the title compound (98mg; crude material used directly in the next step), m/z [M+H]+: 205.9 / 207.9 / 210.1. Retention time 0.89 min (LC/MS method 3).
7-(6-chloro-pyridin-2-ylmethoxy)-heptan-1-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With N-Bromosuccinimide; dibenzoyl peroxide; In tetrahydrofuran; tetrachloromethane; hexane; toluene;
EXAMPLE 36 (2E,4E) N-Isobutyl 11-(6'-chloro-2'-pyridylmethoxy)-3-methylundeca-2,4-dienamide 6-Chloro-2-methylpyridine (20 g), (Ex Aldrich), N-bromosuccinimide (31 g), benzoyl peroxide (570 mg) and tetrachloromethane (250 ml) were heated together under reflux and under irradiation from a powerful lamp for 6 hours. After standard work-up and purification by column chromatography (silica; 5% ether in hexane), 6-chloro-2-bromomethylpyridine (25 g,) was obtained. Sodium hydride (0.109 mol.) was added to 1,7-heptanediol (0.218 mol.) in toluene. After heating under reflux for 3 hours, dry tetrahydrofuran was added, followed by 6-chloro-2-bromomethylpyridine (0.073 mol). After heating under reflux for 4 hours, the cooled mixture was worked-up and purified by column chromatography (silica; 1'1 ether: hexane) to give 7-(6-chloro-2-pyridylmethoxy)-heptan-1-ol (12 g).
With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; hexane;
A. 2-Chloro-6-dimethylaminomethylpyridine To 2-chloro-6-methylpyridine (38.3 g, 0.30 mole) in 300 ml of carbon tetrachloride is added N-bromosuccinimide (67.0 g, 0.375 mole) and benzoyl peroxide (1.0 g). The mixture is stirred at reflux for 22 hours. Then it is cooled to 10 and is filtered. Into the carbon tetrachloride solution of crude 2-chloro-6-bromomethylpyridine is bubbled dimethylamine with ice bath cooling. The mixture is allowed to stand at room temperature overnight. After removal of the dimethylamine hydrobromide by filtration the carbon tetrachloride filtrate is concentrated in vacuo to a dark oil. The oil is taken up in hexane and the product is extracted into 6 N hydrochloric acid (0.30 mole). The acid extract is made alkaline with sodium hydroxide and the product is extracted into benzene. After removal of the benzene the product is distilled. The yield is 42%, b.p. 108-110 at 3.3 mm, n25D 1.5206.
Manufacturing Example 52-1-1 (6-Chloro-pyridin-2-yl)-methanol; To a mixture of 2-chloro-6-methylpyridine (1.0 g, 7.84 mmol) and dichloromethane (20 mL) was added m-chloroperbenzoic acid (3.5 g, 13.2 mmol) on an ice bath, which was stirred for 1.5 hours at 40 C. Water and sodium hydrogencarbonate were added to the reaction mixture, which was then extracted with dichloromethane. The organic layer was separated, washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure. Acetic anhydride (20 mL) was added to the resulting residue and stirred for 1 hour at 100 C. The reaction mixture was cooled to room temperature and concentrated under a reduced pressure. A 5 N aqueous sodium hydroxide solution (4 mL, 20.1 mmol) was added to a mixture of the resulting residue and methanol (20 mL) on an ice bath, which was stirred for 30 minutes. Water was added to this mixture, which was then extracted with ethyl acetate. The organic layer was separated, washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=3:1) to obtain the title compound (200.0 mg, 18%).1H-NMR Spectrum (CDCl3) delta (ppm): 3.08 (1H, brs), 4.75 (2H, d, J=5.2 Hz), 7.23-7.27 (2H, m), 7.64-7.69 (1H, m).
With sodium hydroxide; acetic anhydride; 3-chloro-benzenecarboperoxoic acid; In hydrogenchloride; methanol; dichloromethane;
a 2-Chloropyridine-6-methanol m-Chloroperbenzoic acid (50%) (16.2 g, 94 mmol) was added over 0.75 h to a solution of 2-chloro-6-methylpyridine (5 g, 39 mmol) in dichloromethane (100 ml) at 0 C., and the mixture stirred at room temperature overnight. Further mCPBA (2.7 g, 15 mmol) in dichloromethane (20 ml) was added and stirred for 2 h. Sodium hydroxide solution (4M, 15 ml) was added and the organic layer separated, dried (MgSO4) and evaporated in vacuo to give the N-oxide (5.13 g). The N-oxide (7.74 g,) was added slowly to acetic anhydride (15 ml) at 110 C. with stirring. The mixture was heated at 110 C. for 2 h, cooled to room temperature and distilled in vacuo to give the acetate (4.8 g), bp 98-104 C. at 1.8 mbar. A solution of the acetate (4.8 g) in methanol/HCl solution (1:1) was stirred for 5 h at room temperature. The mixture was basified by addition of sodium hydroxide solution (1 M), and extracted into dichloromethane. The organic extracts were washed with brine (*1), dried (MgSO4) and evaporated in vacuo and the residue flash chromatographed on silica gel, eluding with 2% methanol/dichloromethane to give the title-alcohol (2.02 g), 1H NMR (250 MHz, CDCl3), 6 4.75 (2H, s, CH2), 7.24 (2H, m, 2 of Ar-H) 7.66 (1H, t, J=7.7 Hz, Ar-H); MS (ES30) m/e 144 [MH]+.
Reference example 6: (-chloro-pyridin-2-yl)-acetic acid ethyl ester. n-Butyl lithium (23% in hexane, 13.2 mL, 47.3 mmol) was added dropwise to a cold solution (-70 C) of 2-chloro-6-methyl-pyridine (5.0 g, 39.4 mmol) in tetrahydrofuran (30 mL) and stirred for 30 min at -70 0C. Diethyl carbonate (5.75 mL, 47.3 mmol) was added slowly and the reaction mixture stirred for 30 min at -70 C before warming to room temperature and stirring for a further Ih. The reaction mixture was quenched into saturated ammonium chloride solution and extracted with ethyl acetate. The organic layer was washed with water and brine, then dried over sodium sulfate, filtered and concentrated to yield the crude compound which was purified by column chromatography over silica gel (100-200 mesh), using 9 % ethyl acetate in petroleum ether as eluent, to afford (6-chloro-pyridin-2-yl)-acetic acid ethyl ester (2.21 g, 28 %) as an oil.
6-methyl-2-methylaminopyridine was prepared using the following procedure: A mixture of 2-chloro-6-methylpyridine (2.56 g, 20 mmol) in 50 ml of a 6N solution of methylamine in methanol was heated in a pressure vessel at 1400C for 48 hours. The resulting mixture was concentrated and the residue was taken in dichloromethane and treated with ammonium hydroxide. The organic layer was washed with brine, dried and evaporated to give the desired compound. NMR Spectrum (500 MHz, CDC13) 2.37 (s, 3H), 2.88 (s, 3H), 4.58 (bs, IH), 6.19 (d, IH), 6.45 (d, IH), 7.35 (t, IH).
To a stirred a solution of diisopropylamine (5.3 mL, 37.6 mmol) in anhydrous THF (100 mL) mixture was added at -78 C n-butyllithium (13.8 mL, 34.4 mmol, 2.5 M solution in hexanes) dropwise. The resulting mixture was stirred for 1 hr at -78 C before 2-chloro-6-methylpyridine (3.4 mL, 31.3 mmol) and tetramethylethylenediamine (4.7 mL, 31.3 mmol) were added. The reaction mixture was then allowed to warm to 0 C over 2 hrs. The reaction mixture was re-cooled to -78 C before dimethyl carbonate (7.9 mL, 93.9 mmol) was added and the resulting solution was allowed to warm slowly to room temperature overnight. Reaction was quenched with the addition of saturated aq. ammonium chloride and extracted with EtOAc. The combined organic extracts were washed further with water and brine, dried (Na2S04), filtered and and the filtrate concentrated in vacuo. The residue thus obtained was purified on silica gel eluting with a solvent gradient of 0 to 50% EtOAc in hexanes to afford methyl 2-(6-chloropyridin-2-yl)acetate.
(19-1) 2-Chloro-6-methylpyridine (0.96 mL, 8.1 mmol) was suspended in a 0.15 mol/L disodium hydrogen phosphate aqueous solution (16 mL). Thereafter, a solution prepared by suspending bromine (0.46 mL, 8.9 mmol) in a 0.15 mol//L disodium hydrogen phosphate aqueous solution (16 mL) was added dropwise to the suspension at room temperature over 1 hour. The reaction solution was stirred at the same temperature as described above overnight. Thereafter, the reaction solution was extracted with methylene chloride (30 mL) three times. Organic layers were gathered. The resultant was dried over anhydrous magnesium sulfate and was then filtrated, followed by vacuum concentration. The obtained residue was purified by silica gel column chromatography (SiO2 30 g, hexane:ethyl acetate=99:1 to 95:5), so as to obtain 506 mg of 3-bromo-2-chloro-6-methoxy-pyridine.
With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; potassium carbonate In N,N-dimethyl-formamide at 120℃; for 7h; Schlenk technique; Inert atmosphere;
Tertiary Phosphine Oxides (TPOs) 2-4; General Procedure
General procedure: An oven-dried Schlenk flask was evacuated and back-filled with argon three times. (Hetero)aryl (di)halide (1 equiv), base (1.5 equiv per halogen) and a solution of SPO (1.2 equiv per halogen) in anhydrous solvent (5 mL/mmol per halogen) were added to the flask. The solution was bubbled with argon for 10 min and Pd(OAc)2 (1 mol% per halogen) and ferrocene-based bidentate phosphine ligand (2 mol% per halogen) were added to the flask simultaneously [2.5 mol% Pd(OAc)2 per halogen and 5 mol% dppf per halogen for compounds 2j, 2l, 2r, 2t, 2w]. The resulting mixture was heated at the indicated temperature for the given time. Workup procedures are described below for two different conditions. Final purification of crude products was achieved by column chromatography on silica gel (40-60 μm) using CH2Cl2-MeOH as eluent. Reaction scale and yields are shown in Table 1 (2a-w), Scheme 1 (3a-h) and Scheme 2 (4a-g). Notice that all compounds with two phosphine oxide groups are beige-to-brown solids or slowly solidifying viscous brown oils. Conditions I: ligand: dppf, solvent: DMF, base: Cs2CO3 (2d-n, 2q, 2r, 2t-w, 4a-g) or K2CO3 (3a-h), temperature: 120 °C, time: 7 h (20 h for 2j, 2l, 2r, 2w). Workup: after cooling, the reaction mixture was poured into a fourfold excess of brine. The mixture was extracted three times with CH2Cl2 (40 mL/mmol each). The combined organic layers were washed with brine to remove traces of DMF, dried over Na2SO4 and then evaporated to dryness. Conditions II: ligand: dippf, solvent: toluene, base: t-BuOK, temperature: 110 °C, time: 7 h. Workup: after cooling, the reaction mixture was evaporated to dryness. Then, the mixture was diluted with CH2Cl2 (40 mL/mmol) and washed with water and brine (40 mL/mmol). The organic layer was dried over Na2SO4 and the CH2Cl2 was removed under reduced pressure.
80%
With potassium phosphate; 1,3-bis[(diphenylphosphino)propane]dichloronickel(II) In 1,4-dioxane at 100℃; Inert atmosphere;
20%
With potassium <i>tert</i>-butylate In acetonitrile at 20℃; for 6h; Inert atmosphere; Irradiation;
With (1,5-cyclooctadiene)(methoxy)iridium(l) dimer; 4,4'-di-tert-butyl-2,2'-bipyridine; In hexane; at 80℃; for 17.0h;Inert atmosphere;
2-Chloro-6-methylpyridine 4a (5 g, 39.19 mmol, prepared by a known method "Journal of Chemical Research-Part S, 1996, 4, 194-195"),4,4,4',4',5,5,5',5'-octamethyl-2,2'-bis(1,3,2-dioxaborolane)(10.95g, 43.11mmol), (1,5-cyclooctadiene)methoxy ruthenium(I) dimer (779 mg, 1.18 mmol) and 4,4'-di-tert-butyl-2,2'-dipyridine (631 mg, 2.35 mmol) were dissolved in 125 mL of n-hexane, heated to 80 C and stirred for 17 hours. The reaction was stopped, cooled to room temperature and concentrated under reduced pressure.The residue was purified by thin layer chromatography using a developing solvent system B.The title compound 4b (4.9 g, yield: 49.31%) was obtained.
With manganese; bis(bipyridine)nickel(II) bromide; trifluoroacetic acid; In N,N-dimethyl-formamide; at 20℃;Inert atmosphere; Schlenk technique;
II. General Procedure for Preparation of 2,6-Disubstituted Pyridines2To a solution of NiBr2(bpy) (bpy = 2,2?-bipyridine, 0.5 mmol, 10 mol%) andmanganese powder (11.5 mmol) in DMF (8 mL) were successively added at roomtemperature the aryl bromide (5 mmol), 2-chloro-6-methylpyridine (6.5 mmol) andtrifluoroacetic acid (100 muL), causing an immediate rise in temperature and colorchange to dark grey. The medium was the stirred at room temperature until completeconversion of aryl bromide. The reaction mixture was poured into a saturated aqueoussolution of NH4Cl and extracted with EtOAc. The organic layer was washed with asaturated aqueous solution of NaCl and dried over Na2SO4. Evaporation of solvent andpurification by flash column chromatography on silica gel (hexane/EtOAc) afforded thecoupling product. Dragendorff?s reagent was used as a TLC coloring reagent fordetection of pyridines.2-Methyl-6-phenylpyridine, 2-hexyl-6-phenylpyridine and 3-methyl-2-phenylpyridineare commercially available (TCI, Wako).
6-methyl-N-(3-phenylpropyl)pyridine-2-amine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
92%
With bis[chloro(1,2,3-trihapto-allylbenzene)palladium(II)]; TPGS-750-M; sodium t-butanolate; tert-butyl XPhos In water at 50℃; for 16h; Inert atmosphere; Green chemistry;
81%
With bis(η3-allyl-μ-chloropalladium(II)); sodium t-butanolate; tert-butyl XPhos In water at 50℃; for 3h; Inert atmosphere;
1.7.2 1.7 Preparation of 6-methyl-N-(3-phenylpropyl)pyridine-2-amine
General procedure: An amine (1.2 eq), an aryl bromide (1.0 eq), [(7i-allyl)PdCl]2 catalyst (0.005 eq), a phosphine ligand (0.020 eq) and a base (1.50 eq) were added under an Argon atmosphere into a 5.0 mL microwave vial containing a magnetic stir bar and Teflon- lined septum. HPMC in water solution (40-60 cps, 3 ml of 2 wt % in degassed Millipore water) was added under a positive flow of argon (however, any liquid components were always added after the solvent). The reaction mixture was stirred at 1200 rpm for the indicated time at the indicated temperature. To the reaction mixture were added ethyl acetate and saturated aqueous sodium sulfate solution. The organic phase was separated from the solid. The solid was washed three times with ethyl acetate. The combined ethyl acetate phases were dried in vacuo and the residue was further purified by flash chromatography on silica gel (0-30% ethyl acetate/heptane).; According to the general procedure II, 3-phenylpropylamine (162 mg, 1.20 mmol), 2-chloro-6-methylpyridine (128 mg, 1.00 mmol), [(7i-allyl)PdCl]2 catalyst (5.7 mg, 0.011 mmol), di-tert-butyl(2',4',6'-triisopropyl-[l, -biphenyl]-2-yl)phosphine (t- BuXPhos) ligand (18.8 mg, 0.044 mmol), NaO-t-Bu (145 mg, 1.50 mmol) and a HPMC-solution (40-60 cps, 1 ml of 2 wt % in degassed Millipore water) were stirred at 1200 rpm for 3 h at 50°C. To the reaction mixture were added 20 ml of ethyl acetate and 3 ml of saturated aqueous sodium sulfate solution. The organic phase was separated from the solid. The solid was washed three times with ethyl acetate. The combined ethyl acetate phases were dried in vacuo and the residue was further purified by flash chromatography on silica gel (0-100% ethyl acetate/cyclohexane). The desired product was obtained as an off-white solid (183 mg, 81% yield). ESI-MS: m/z (%): 227.20 (100, [M+H]+). 1H NMR (600MHz,
With tris-(dibenzylideneacetone)dipalladium(0); sodium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In toluene; at 150℃; for 0.5h;Microwave irradiation;
Specifically, a mixture of <strong>[30235-26-8]4-(pyridine-2-yl)thiazole-2-amine</strong> (53 mg, 0.30 mmol), 2-chloro- 6-methylpyridine (27.7 ul, 0.25 mmol), powdered a2C03 (39 mg, 0.37 mmol), Xantphos (25 mg, 0.04 mmol) and Pd2(dba)3 (20 mg, 0.02 mmol) in toluene (1 ml) was heated at 150C for 30 min under microwave irradiation. After cooled to room temperature the mixture was diluted with AcOEt and filtered to remove insoluble. The filtrate was evaporated. The residue was purified by preparative reversed phase HPLC (C18, 50-95% acetonitrile in water) to give compound 7 (17 mg, 25% yield). XH NMR (300 MHz, DMSO- d6) delta 1 1.39 (s, 1H), 8.62 - 8.53 (m, 1H), 7.96 (dd, J= 7.7, 0.8, 1H), 7.87 (td, J= 7.9, 1.8, 1H), 7.65 (s, 1H), 7.60 (t, J= 7.8, 1H), 7.35 - 7.25 (m, 1H), 6.89 (d, J= 8.2, 1H), 6.80 (d, J = 7.3, 1H), 2.47 (s, 3H).
2-methyl-6-(2,3,5,6-tetrafluoro-4-(trifluoromethyl)phenyl)pyridine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
70%
With N-methyl-2-phenyl-3-(dicyclohexylphosphino)-1H-indole; palladium diacetate; sodium phosphate; Trimethylacetic acid In dichloromethane; N,N-dimethyl acetamide at 100℃; for 24h; Schlenk technique; Inert atmosphere;
With potassium carbonate; In 1-methyl-pyrrolidin-2-one; at 150℃; for 18h;
[000747j A mixture of Compound 103A (4.5 g, 21.8 mmol), Compound 103B (3.43 g, 21.8 mmol), and K2C03 (7.5 g, 54.4 mmol) in DMF (18 mL) was stirred at 150 C for 18 h. The reaction mixture was treated with water and extracted with ethyl acetate (150 mL x 3). The extracts were washed with water (50 mL), dried over sodium sulfate, concentrated, and purified with flash column chromatography on silica gel (ethyl acetate in petroleum ether, from 5% to 20% v/v) to furnish Compound 103C. [0008031 Compound 131C was synthesized, by employing the procedure described forCompound 103C using Compound 131A and 131B in NMP in lieu of Compound 103A and103B in DMF. LC-MS (ESI) mlz: 298 [M+H] ?H-NMR (CDC13, 400 MHz): 5 (ppm) 2.42(s, 3H), 6.67 (d, J= 8.4 Hz, 1H), 6.90 (d, J 7.2 Hz, 1H), 7.29 (d, J 9.2 Hz, 1H), 7.33 (d, J= 7.2 Hz, 2H), 7.60 (t, J 8.0 Hz, 1H).
With palladium diacetate; sodium carbonate; XPhos; In 1,4-dioxane; water; at 80.0℃; for 2.08333h;Inert atmosphere; Sealed tube; Microwave irradiation;
Example A.5 Preparation of intermediate (8) In a microwave vial (20 mL volume), <strong>[913835-32-2]3-carboxy-4-chlorophenylboronic acid</strong> (0.218 g, 0.92 mmol, 2.0 eq), 2-chloro-6-methylpyridine (0.05 mL, 0.46 mmol, 1 eq), palladiumacetate (0.017 g, 0.08 mmol, 0.17 eq), Xphos (0.09 g, 0.157 mmol, 0.34 eq) andsodium carbonate (0.147 g, 3 mmol, 3 eq) were suspended in degassed 10/1 dioxane/H20 solution (2.5 mL). The vial was sealed, flushed with nitrogen and mechanically stirred for 5 mm. The mixture was then heated for 2 h at at 80C in a microwave reactor. The resulting black suspension, was evaporated in vacuo, water (20 mL) was added, followed by 1/1 DCM/AcOEt (20 mL) and 37% HC1 (10 mL). The resulting solution was poured in a separating funnel and the acqueous layer separated and evaporated. The resulting white powder was treated with MeOH (3 mL), filtered and finally evaporated, affordingintermediate (8) as white powder (0.11 g, yield 95%).
1-(4-bromophenyl)-3-(6-methylpyridin-2-yl)pyrrolidin-2-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
44%
With sodium hexamethyldisilazane In tetrahydrofuran at -10 - 0℃; for 3h;
37
To a stirred solution of 1-(4-bromophenyl) pyrrolidin-2-one (2.0 g, 8.3 mmol, 1.0 equiv) and 2-chloro-6-methylpyridine (1.8 ml, 16.6 mmol, 2.0 equiv) in THF (50 ml) was added NaHMDS (1 M in THF) (17 ml, 16.6 mmol, 2.0 equiv) at -10°C and stirred for 3h at 0°C. Reaction mixture was monitored by LCMS and TLC. After 3h, reaction mixture was quenched with sat. NH4CI solution and extracted with EtOAc (3 x 100ml_). Combined organic layers were washed with water and brine solution and dried over Na2S04, filtered and concentrated to get crude product. Crude product was purified by flash chromatography on Silica gel and compound was eluted with 30% EtOAc/Hexane, yield (1.1 g, 44 %), off-white solid. LC-MS (ES) m/z = 331.0, 333.0 [M+H]+. H NMR (400 MHz, CDCIs) δ 2.43 (s, 3 H), 2.46 - 2.49 (m, 2 H), 3.87 - 4.05 (m, 3 H), 7.12 - 7.18 (m, 2 H), 7.55 (d, J=8.8 Hz, 2 H), 7.62 - 7.68 (m, 3 H).
A 2.5 M solution of BuLi in hexanes (11 mmol, 4.4 mL) was added dropwise to a stirred solution of 2-chloro-6-methylpyridine (1.40 g,11 mmol, 1.2 mL) in THF (15 mL) at -78 C. The resulting red solution was stirred at -78 C for 10 min then warmed to -10 C for 20 min. The mixture was then cooled to -78 C, and a solution of Cy2CO (2.56 g, 13.2 mmol, 2.6 mL) in THF (2 mL) was added. The mixture was stirred at -78 C for 30 min, then SOCl2 (2.12 g, 17.8 mmol, 1.3 mL) was added. The milky mixture was warmed to 0 C for 30 min and then the reaction was quenched with sat. aq NH4Cl (10 mL). The mixture was diluted with EtOAc (20 mL), and the layers were separated. The organic layer was washed with brine (20 mL), dried (Na2SO4), and concentrated in vacuo. Flash column chromatography [silica gel, hexanes-EtOAc (5:1)] gave a mixture of pyridines 3 as a white amorphous solid; yield: 2.87 g (85%, ~2:1 mixture of regioisomers by 1H NMR).
(2-(6-methylpyridin-2-yl)phenyl)methanol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
85%
With C37H44ClN2O3PPd; caesium carbonate; In water; at 100℃; for 12h;Schlenk technique; Inert atmosphere;
General procedure: In a Schlenk tube, a mixture of the required amount of catalyst, plus the aryl chloride (1.0 mmol), aryl boronic acid (1.5 mmol) and the selected base (2.0 mmol) in water was evacuated and charged with nitrogen. The reaction mixture was heated at 100°C for 12 h. After cooling, the mixture was extracted with CH2Cl2 and the extract was evaporated. The resulting residue was purified by flash chromatography on silica gel using a mixture of CH2Cl2/ethyl acetate (5/1) as eluent. The known products 5, 6a [17,18], 6b [22], 6c [23], 6e [24], 6g [19], 6h [25] and 7a [26] were characterized by comparison of data with those in the literature. The products 6d, 6f and 7b?h were new compounds and characterized by elemental analysis, MS, 1H and 13C NMR.
2-(4-methoxy-3-nitrophenyl)-6-methylpyridine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
0.38 g
With potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In 1,2-dimethoxyethane; water at 80℃; for 6.5h;
27 Reference Production Example 27
Reference Production Example 27 (1348) A mixture of 0.46 g of 2-chloro-6-methylpyridine, 1.00 g of a 4-methoxy-3-nitro-phenylboronic acid pinacol ester, 0.29 g of [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloride dichloromethane adduct, 1.52 g of tripotassium phosphate, 40 mL of 1,2-dimethoxyethane, and 5 mL of water was stirred at 80° C. for 6.5 hours. After cooling, water was added and the reaction mixture was filtered, and then the filtrate was extracted with ethyl acetate. The organic layer was washed with water and a saturated saline solution, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue thus obtained was subjected to silica gel column chromatography to obtain 0.38 g of 2-(4-methoxy-3-nitrophenyl)-6-methylpyridine (referred to as CA27). (1349) 1H-NMR (CDCl3) δ: 2.62 (3H, s), 4.01 (3H, s), 7.12 (1H, d, J=7.8 Hz), 7.17 (1H, d, J=8.8 Hz), 7.50 (1H, d, J=7.8 Hz), 7.66 (1H, t, J=7.8 Hz), 8.21 (1H, dd, J=8.8, 2.3 Hz), 8.52 (1H, d, J=2.3 Hz).
With tetrabutylammomium bromide; potassium carbonate; palladium dichloride; XPhos In water at 120℃; Inert atmosphere; Schlenk technique; Green chemistry;
Typical procedure for deacetonative coupling of aryl propargylic alcohols with aryl chlorides in water
General procedure: To a 25-mL Schlenk tube equipped with magnetic stir bar, aryl chloride (0.2 mmol), aryl propargylic alcohol (0.3 mmol), K2CO3 (2.0 equiv.), TBAB (1.0 equiv.), PdCl2 (2 mol%), and Xphos (4 mol%) were added in turn, then 2 mL H2O was added, and then the solution was refluxed for 24 h under N2 atmosphere. After the reaction was completed, the mixture was extracted with EtOAc or CH2Cl2. The combined organic layer was dried with anhydrous Na2SO4 and evaporated in vacuum. The crude product was purified by flash chromatography on silica gel using hexane/ethyl acetate as the eluent to afford the desired product.
1-[2'-(6''-methyl)pyridyl]-4-(N-Boc-N-methyl)aminopiperidine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
89%
With potassium tert-butylate; palladium diacetate; DavePhos; In toluene; at 120℃; for 12h;Inert atmosphere;
General procedure: An oven-dried reaction flask, equipped with a reflux condenser was charged with heteroaryl chloride (1.0 mmol), 4-(N-Boc-N-methyl)aminopiperidine (1.3 equiv.), Pd(OAc)2 (3 mol%), DavePhos (3 mol%), t-BuONa (1.2 equiv.). The flask was sealed, and was evacuated and backfilled with argon for three times. Then 3 mL toluene was added to the system with a syringe. The reaction mixture was stirred at 120 C for 12 h. After cooling to the room temperature, the resulting residue was filtered through a plug of silica gel and washed with ethyl acetate. The mixture was then poured into water and extracted. The combined organic layers were washed with brine, dried over MgSO4, and filtered. The solvent was removed under vacuum. The residue was purified by flash column chromatography to afford the desired product.
With dichloro(benzene)ruthenium(II) dimer; sodium carbonate; Trimethylacetic acid; In 1-methyl-pyrrolidin-2-one; at 220℃; for 1h;Microwave irradiation; Inert atmosphere;
General procedure: In a sample vial for microwave synthesizer manufactured by Biotage, 0.155 g of Exemplified compound (1) -1, 0.908 g of Exemplified compound (2) -1, 20.4 mg of pivalic acid, 0.636 g of sodium carbonate, 5.0 mL of NMP as a solvent and 30.6 mg of [RuCl2 (eta6-C6H6)] 2 as a catalyst were added, and after bubbling with nitrogen gas, the cap was capped with a dedicated cap and mounted in a microwave device and heated at 220 C. for 1 hour. It was stirred. After the reaction, the reaction mixture was cooled to room temperature, the solvent NMP was distilled off under reduced pressure, and the residue was purified by a silica gel chromatogram to obtain 0.990 g (yield 93%) of a desired compound, Exemplified Compound (3) -8.
With potassium <i>tert</i>-butylate; C51H40BrCuN3OP2(1+)*F6P(1-) In 1,4-dioxane at 110℃; for 12h; Schlenk technique; Inert atmosphere;
General procedure for the amination
General procedure: In a Schlenk tube, a mixture of the catalyst 1 (0.5 mol%),2-N-heteroaryl chloride (1.0 mmol), pyrazole (1.1 mmol),and KOtBu (2.0 mmol) in dioxane (3 mL) was evacuatedand charged with nitrogen. The reaction mixture was heatedat 110 °C for 12 h. After being cooled and quenched withwater, the mixture was extracted with CH2Cl2. The solventwas evaporated and the resulting residue was purified by flash chromatography on silica gel.
5,5-dimethyl-3-((6-methylpyridin-2-yl)methyl)cyclohex-2-enone[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
87%
With 2-(2,6-dimethoxyphenyl)-1-methyl-3-(diphenylphosphino)-1H-indole; palladium diacetate; lithium tert-butoxide In 1,4-dioxane at 100℃; for 1h; Schlenk technique; Inert atmosphere;
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