* 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 water; iodine; oxygen; sodium carbonate In 1,4-dioxane at 100℃; for 60 h; Schlenk technique; Sealed tube
General procedure: Under air, a 20 mL of Schlenk tube equipped with a stir bar was charged with indole 1 (0.2 mmol, 1 equiv),TMEDA (75 µL, 0.5 mmol, 2.5 equiv), Na2CO3 (42.4 mg, 0.4mmol, 2.0 equiv), 1,4-dioxane (0.5 mL) and H2O (100 µL). Then I2 (101.5 mg, 0.4 mmol, 2.0 equiv) was added and the tube was sealed with a rubber plug and charged with O2. The reaction mixture was stirred at 100 °C for 36 h in oil bath. After cooling to room temperature, the resultant mixture was evaporated with EtOAc (20 mL) under reduced pressure and the residue was purified by flash column chromatography on a silica gel to give the products.
With sodium hydrogencarbonate In N,N-dimethyl-formamide; mineral oil
a. 5-Methoxy-1-methylindole-3-carboxaldehyde (43) 5-Methoxyindole-3-carboxaldehyde (300 mg, 1.71 mmol) was added in portions over 5 min to a suspension of sodium hydride (82 mg, 2.05 mmol, 60percent dispersion in mineral oil) in DMF (8 mL) stirring under argon. The mixture was stirred for 30 min, methyl iodide (0.13 mL, 2.05 mmol) was added and the mixture was stirred for 1 h. Sodium bicarbonate (10percent, 40 mL) was added and the mixture was extracted with EtOAc (4*). The combined organic layers were washed with sodium bicarbonate (10percent, 2*) and saturated NaCl, dried (MgSO4), filtered and evaporated. Column chromatography of the crude product (50:50 EtOAc:hexanes) afforded 43 (320 mg, 99percent) as a light yellow solid; Rf=0.35 (50:50 EtOAc:hexanes); mp=130-132° C.; lit mp=132-133° C.53; 1H NMR (CDCl3): δ 9.95 (s, 1H), 7.79 (d, 1H, J=2.4 Hz), 7.62 (s, 1H), 7.25 (d, J=8.8 Hz), 6.96 (dd, 1H, J=2.4 and 8.9 Hz), 3.90 (s, 3H), 3.85 (s, 3H).
1.03 g
Stage #1: With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.166667 h; Inert atmosphere Stage #2: at 0 - 40℃; for 0.5 h; Inert atmosphere
5-methoxy-indole 22 (1.78 g, 9.40 mmol) was added gradually and under dry argon to a suspension of NaH (0.564 g of a 60percent dispersion, 14.11 mmol) in dry DMF (4 mL). The suspension was stirred at room temperature for 10 min and cooled to 0 °C, and MeI (0.81 g, 5.71 mmol) was added over 5 min. The solution was then heated at 40 °C for 30 min, cooled, poured into cold water. The mixture was extracted with EtOAc (2× 150 mL), dried and evaporated. The residue was used without purification (1.03 g, 95percent). 1H NMR (300 MHz, DMSO-d6): δ (ppm) 9.72 (s, 1H), 8.45 (s, 1H), 7.82 (d, J = 9.1 Hz, 1H), 7.37 (d, J = 9.1 Hz, 1H), 3.93 (s, 3H), 3.91 (s, 3H); MS (ESI) m/z: 190.1 [M+H]+.
Reference：
[1] Tetrahedron, 2005, vol. 61, # 7, p. 1793 - 1801
[2] Organic Letters, 2013, vol. 15, # 11, p. 2636 - 2639
[3] Patent: US2003/8850, 2003, A1,
[4] Journal of Medicinal Chemistry, 2018, vol. 61, # 14, p. 6261 - 6276
[5] Chemical Biology and Drug Design, 2015, vol. 86, # 4, p. 731 - 745
[6] Heterocyclic Communications, 2010, vol. 16, # 2-3, p. 195 - 199
[7] Journal of Medicinal Chemistry, 1997, vol. 40, # 15, p. 2335 - 2346
[8] Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 18, p. 3111 - 3114
[9] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 6, p. 1793 - 1798
[10] Patent: US2004/9983, 2004, A1, . Location in patent: Page/Page column 105
[11] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 8, p. 2586 - 2590
[12] European Journal of Medicinal Chemistry, 2015, vol. 99, p. 125 - 137
[13] RSC Advances, 2015, vol. 5, # 83, p. 68128 - 68135
[14] Journal of Medicinal Chemistry, 2016, vol. 59, # 11, p. 5264 - 5283
[15] ChemMedChem, 2016, vol. 11, # 13, p. 1446 - 1458
[16] RSC Advances, 2016, vol. 6, # 36, p. 30412 - 30424
[17] European Journal of Medicinal Chemistry, 2017, vol. 132, p. 310 - 321
[18] Organic and Biomolecular Chemistry, 2017, vol. 15, # 35, p. 7404 - 7410
[19] Patent: WO2018/31662, 2018, A1, . Location in patent: Page/Page column 176
[20] European Journal of Medicinal Chemistry, 2018, vol. 156, p. 722 - 737
3
[ 10601-19-1 ]
[ 77-78-1 ]
[ 39974-94-2 ]
Reference：
[1] Archiv der Pharmazie, 1988, vol. 321, # 11, p. 823 - 826
[2] Heteroatom Chemistry, 2012, vol. 23, # 1, p. 41 - 48
[3] Synthetic Communications, 2012, vol. 42, # 12, p. 1746 - 1759
[4] Journal of Chemical Sciences, 2011, vol. 123, # 5, p. 609 - 614
4
[ 1006-94-6 ]
[ 39974-94-2 ]
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 6, p. 1793 - 1798
[2] Organic Letters, 2013, vol. 15, # 11, p. 2636 - 2639
[3] Angewandte Chemie - International Edition, 2014, vol. 53, # 41, p. 11051 - 11055[4] Angew. Chem., 2014, vol. 126, # 41, p. 11231 - 11235,5
[5] European Journal of Medicinal Chemistry, 2015, vol. 99, p. 125 - 137
[6] RSC Advances, 2015, vol. 5, # 83, p. 68128 - 68135
[7] Chemical Biology and Drug Design, 2015, vol. 86, # 4, p. 731 - 745
[8] Journal of Medicinal Chemistry, 2016, vol. 59, # 11, p. 5264 - 5283
[9] ChemMedChem, 2016, vol. 11, # 13, p. 1446 - 1458
[10] European Journal of Medicinal Chemistry, 2017, vol. 132, p. 310 - 321
[11] Organic and Biomolecular Chemistry, 2017, vol. 15, # 35, p. 7404 - 7410
[12] RSC Advances, 2016, vol. 6, # 36, p. 30412 - 30424
[13] European Journal of Medicinal Chemistry, 2018, vol. 156, p. 722 - 737
5
[ 2521-13-3 ]
[ 68-12-2 ]
[ 39974-94-2 ]
Reference：
[1] Heterocycles, 1988, vol. 27, # 7, p. 1671 - 1678
[2] Organometallics, 2010, vol. 29, # 4, p. 1032 - 1040
[3] Angewandte Chemie - International Edition, 2014, vol. 53, # 41, p. 11051 - 11055[4] Angew. Chem., 2014, vol. 126, # 41, p. 11231 - 11235,5
6
[ 2521-14-4 ]
[ 39974-94-2 ]
Reference：
[1] European Journal of Organic Chemistry, 2018, vol. 2018, # 47, p. 6624 - 6628
7
[ 2521-13-3 ]
[ 67-68-5 ]
[ 39974-94-2 ]
Reference：
[1] Organic and Biomolecular Chemistry, 2013, vol. 11, # 41, p. 7092 - 7095
8
[ 2521-13-3 ]
[ 39974-94-2 ]
Reference：
[1] European Journal of Organic Chemistry, 2018, vol. 2018, # 47, p. 6624 - 6628
9
[ 487-89-8 ]
[ 75-18-3 ]
[ 39974-94-2 ]
Reference：
[1] Asian Journal of Chemistry, 2013, vol. 25, # 15, p. 8741 - 8748
With hydroxylamine hydrochloride; In DMF (N,N-dimethyl-formamide); for 1h;Heating / reflux;
<strong>[39974-94-2]5-Methoxy-1-methyl-1H-indole-3-carbaldehyde</strong> [76 g, Reference Example 2(a)] and hydroxylamine hydrochloride (55.9 g) were stirred together in dimethylformamide (900 mL) under reflux for 1 hour. The mixture was allowed to cool, then poured into water and then extracted with ethyl acetate. The combined extracts were washed with water then evaporated to give the title compound (53 g) as a pale brown solid, m.p. 100-104 C. 1H NMR [(CD3)2SO]: delta 8.17 (1H, s); 7.54 (1H, d, J=9.0 Hz); 7.09 (1H, d, J=2.4 Hz); 6.97 (1H, dd, J=9.0 and 2.4 Hz); 3.82 and 3.84 (6H, s).
To a solution of 5-Methoxy-1 -methyl- 1H-indole-3-carbaldehyde (4.5g, 23.8 mmol, in 150 ml DCM) was added BBr3 solution (2 M in DCM, 60 ml, 5 eq) at -10 ºC with stirring for 5 min. The cooling bath was removed and the reaction mixture was slowly warmed up to r.t. The reaction was monitored by TLC (2% MeOH in DCM) and LCMS (after 3.5 h, no starting material remained). The reaction mixture was then cooled to -10 ºC, and 16 ml of MeOH were slowly added. The pH of mixture was adjusted to 8 by adding sat. NaHCO3 and/or 4 N NaOH. The organic solvents were removed under reduced pressure and the remaining aqueous mixture was extracted with ethyl acetate (30 mlx5). The organic layers were combined, washed with brine (10mIx1 ), dried over Mg2SO4, filtered and dried under reduced pressure to give the title compound as 4.06 g purple powder (yield: 97%) EPO <DP n="27"/>that was used without further purification. LCMS (2-85 % ACN/H2O in 7 min): 176.1 (40%). Rf 0.11 (2% MeOH in DCM).
With water; iodine; oxygen; sodium carbonate; In 1,4-dioxane; at 100℃; under 760.051 Torr; for 60h;Schlenk technique; Sealed tube;
General procedure: Under air, a 20 mL of Schlenk tube equipped with a stir bar was charged with indole 1 (0.2 mmol, 1 equiv),TMEDA (75 muL, 0.5 mmol, 2.5 equiv), Na2CO3 (42.4 mg, 0.4mmol, 2.0 equiv), 1,4-dioxane (0.5 mL) and H2O (100 muL). Then I2 (101.5 mg, 0.4 mmol, 2.0 equiv) was added and the tube was sealed with a rubber plug and charged with O2. The reaction mixture was stirred at 100 C for 36 h in oil bath. After cooling to room temperature, the resultant mixture was evaporated with EtOAc (20 mL) under reduced pressure and the residue was purified by flash column chromatography on a silica gel to give the products.
General procedure: Titanium tetrachloride (1.90 g, 10 mmol) was slowly added to100 mL of anhydrous THF at 0 C, followed by addition of 5 mmol of the aldehyde (1) and stirred for 10 min, then ethyl 2-(3-bromopyridin-2-yl)acetate (2) (1.47 g, 6 mmol) was added. Subsequently, a solution of pyridine (3.16 g, 40 mmol) in 25 mL of anhydrous THF was added dropwise during a period of 30-60 min at 0 C. The reaction mixture was then stirred for 1 h at room temperature and refluxed for 24 h. After that the mixture was poured on to crashed ice and extracted with ethyl acetate (4 30 mL). The combined extracts were successively washed with brine, saturated sodium hydrogen carbonate and brine, and then dried over anhydrous MgSO4. The organic phase was filtrated and the solvent was removed in vacuo, the residue was purified by column chromatography (silica gel) using PE/EA (5:1) / DCM/MeOH (50:1) to provide 3.
With sodium metabisulfite; In N,N-dimethyl-formamide; at 110℃; for 4h;
General procedure: A solution of o-phenylenediamine (5.41 g, 50 mmol) in DMF (20 mL) was added dropwise to a suspension of 7-9 (50 mmol) and Sodium pyrosulfite (19.09 g, 100 mmol) in DMF (50 mL). The heterogeneous mixture was stirred at 110 C for 4 h, then cooled and poured onto a lot of ice. A large amount of solid would emerge, and was filtered to give 2-(1-methylindol-3-yl)-benzimidazole (10-12), a yellow powder.
[3-acetyl-11,11-dimethyl-2,5-dioxo-5,11-dihydro-2H-pyrano[2',3':4,5]pyrido[1,2-a]indol-4-yl] difluoridoborate[ No CAS ]
3-[(2E)-3-(5-methoxy-1-methyl-1H-indol-3-yl)prop-2-enoyl]-11,11-dimethyl-2,5-dioxo-5,11-dihydro-2H-pyrano[2',3':4,5]pyrido[1,2-a]indol-4-yl difluoridoborate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
45%
With acetic anhydride; at 60 - 90℃; for 0.5h;
General procedure: Condensation of borodifluoride complex 9 with aldehydes (general procedure). A solution of the corresponding aldehyde(2 mmol) dissolved in acetic anhydride (2 mL) was added toa solution of 3acetyl11,11dimethyl2,5dioxo5,11dihydro2Hpyrano[2,3:4,5]pyrido[1,2a]indole4yl difluoridoborate(9) (0.770 g, 2 mmol) in acetic anhydride (6 mL) at 60 C. Themixture was heated at 90 C for 0.5 h. After cooling, a precipitateformed was filtered off, washed on the filter with acetic acid, andrecrystallized from acetic acid.3{(2E)3[4(Di
7-acetyl-10,10-dimethyl-6-oxo-6,10-dihydropyrido[1,2-a]indol-8-yl difluoridoborate[ No CAS ]
7-[(2E)-3-(5-methoxy-1-methyl-1H-indol-3-yl)prop-2-enoyl]-10,10-dimethyl-6-oxo-6,10-dihydropyrido[1,2-a]indol-8-yl difluoridoborate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
80%
With acetic anhydride; at 60 - 90℃; for 0.5h;
General procedure: A solution of the corresponding aldehyde (2 mmol) dissolved inacetic anhydride (2 mL) was added to a solution of 7acetyl10,10dimethyl6oxo6,10dihydropyrido[1,2a]indol8yl difluoridoborate (4) (0.63 g, 2 mmol) in acetic anhydride (6 mL) at60 C. The mixture was heated at 90 C for 0.5 h. After cooling,a precipitate formed was filtered off, washed on the filter withacetic acid, and recrystallized from acetic acid.
With potassium hydroxide; In ethanol; at 20℃; for 24h;
General procedure: The relevant N-methyl intermediate (3a-c, 2 mmol), acetophenonederivate (2 mmol) and potassium hydroxide (6 mmol) wasdissolved in ethanol (20 mL) and stirred for 24 h. Then the reactionmixture was filtered and washed with water and cold ethanol. Thecrude product was purified by recrystallization from ethanol anddichloromethane to give pure chalcone (4a-q) with yields of34.2-93.1%.
With potassium hydroxide; In ethanol; at 20℃; for 24h;
General procedure: The relevant N-methyl intermediate (3a-c, 2 mmol), acetophenonederivate (2 mmol) and potassium hydroxide (6 mmol) wasdissolved in ethanol (20 mL) and stirred for 24 h. Then the reactionmixture was filtered and washed with water and cold ethanol. Thecrude product was purified by recrystallization from ethanol anddichloromethane to give pure chalcone (4a-q) with yields of34.2-93.1%.
With potassium hydroxide; In ethanol; at 20℃; for 24h;
General procedure: The relevant N-methyl intermediate (3a-c, 2 mmol), acetophenonederivate (2 mmol) and potassium hydroxide (6 mmol) wasdissolved in ethanol (20 mL) and stirred for 24 h. Then the reactionmixture was filtered and washed with water and cold ethanol. Thecrude product was purified by recrystallization from ethanol anddichloromethane to give pure chalcone (4a-q) with yields of34.2-93.1%.
With potassium hydroxide; In ethanol; at 20℃; for 24h;
General procedure: The relevant N-methyl intermediate (3a-c, 2 mmol), acetophenonederivate (2 mmol) and potassium hydroxide (6 mmol) wasdissolved in ethanol (20 mL) and stirred for 24 h. Then the reactionmixture was filtered and washed with water and cold ethanol. Thecrude product was purified by recrystallization from ethanol anddichloromethane to give pure chalcone (4a-q) with yields of34.2-93.1%.
With potassium hydroxide; In ethanol; at 20℃; for 24h;
General procedure: The relevant N-methyl intermediate (3a-c, 2 mmol), acetophenonederivate (2 mmol) and potassium hydroxide (6 mmol) wasdissolved in ethanol (20 mL) and stirred for 24 h. Then the reactionmixture was filtered and washed with water and cold ethanol. Thecrude product was purified by recrystallization from ethanol anddichloromethane to give pure chalcone (4a-q) with yields of34.2-93.1%.
3,3'-(3-phenylprop-2-yn-1,1-diyl)bis(5-methoxy-1-methyl-1H-indole)[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
78%
General procedure: To the ice-cold solution of aldehyde in THF was added, the solution of alkylmagnesium halide or alkyllithium in THF (1.3 eq., at 0 C). The reaction was stirred at 0 C for 1 h, diluted with saturated aq. NH4Cl (10 mL) and ethyl acetate (10 mL). Aqueous layer was extracted with ethyl acetate (2×10 mL). The combined organic layers were washed with brine (10 mL), and dried over Na2SO4. Evaporation of the solvent and purification of the crude mixture by column chromatography (9:1, hexane: EtOAc) gave the corresponding bisindolylmethane derivatives (BIM) up to 92% yields along with the by-product aldehyde.
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