* 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] Archiv der Pharmazie (Weinheim, Germany), 1937, vol. 275, p. 506,511
2
[ 87-51-4 ]
[ 64-17-5 ]
[ 778-82-5 ]
Yield
Reaction Conditions
Operation in experiment
88%
Stage #1: With sulfuric acid In ethanol at 0℃; for 2 h; Reflux Stage #2: With sodium hydroxide In ethanol
Ethyl 1H-indol-3-ylacetate Indol-3-ylacetic acid (1.00 g, 5.71 mmol) was dissolved in 25 ml ethanol and concentrated sulphuric acid (1.0 ml, 18.4 mmol) was added. The mixture was stirred at reflux for 2 h and cooled to 0 ºC in an ice bath before neutralization with 2N sodium hydroxide solution. The organics were evaporated under reduced pressure and the mixture was partitioned between dichloromethane and water. The aqueous phase was extracted twice with dichloromethane and the combined organic were washed with brine, dried over sodium sulphate, filtered and evaporated under reduced pressure to give 1.02 g (5.02 mmol, 88percent) of the title compound as a brown oil. Purity 100percent.1H NMR (300 MHz, CHLOROFORM-d) δ ppm 8.09 (br. s., 1 H), 7.63 (d, J=7.69 Hz, 1 H), 7.35 (d, J=7.69 Hz, 1 H), 7.04 - 7.25 (m, 3 H), 4.17 (q, J=7.14 Hz, 2 H), 3.77 (s, 2 H), 1.26 (t, J=7.14 Hz, 3 H).UPLC/MS (3 min) retention time 1.58 min.LRMS: m/z 204 (M+1).
88%
Stage #1: at 0℃; for 2 h; Reflux Stage #2: With sodium hydroxide In ethanol
lndol-3-ylacetic acid (1 .00 g, 5.71 mmol) was dissolved in 25 ml ethanol and concentrated sulphuric acid (1 .0 ml, 18.4 mmol) was added. The mixture was stirred at reflux for 2 h and cooled to 0 °C in an ice bath before neutralization with 2N sodium hydroxide solution. The organics were evaporated under reduced pressure and the mixture was partitioned between dichloromethane and water. The aqueous phase was extracted twice with dichloromethane and the combined organic were washed with brine, dried over sodium sulphate, filtered and evaporated under reduced pressure to give 1 .02 g (5.02 mmol, 88percent) of the title compound as a brown oil. Purity 100percent. 1 H N MR (300 MHz, CHLOROFORM-d) δ ppm 8.09 (br. s., 1 H), 7.63 (d, J=7.69 Hz, 1 H), 7.35 (d, J=7.69 Hz, 1 H), 7.04 - 7.25 (m, 3 H), 4.17 (q, J=7.14 Hz, 2 H), 3.77 (s, 2 H), 1 .26 (t, J=7.14 Hz, 3 H). UPLC/MS (3 min) retention time 1 .58 min. LRMS: m/z 204 (M+1 ).
82%
for 2 h; Reflux
To the solution of indole-3-acetic acid (1) (0.01 mol) in absolute ethyl alcohol (25 mL), conc. H2SO4 (2 mL) was added. The mixture was refluxed for 2 h. After completion of the reaction (monitored by TLC), the mixture was poured into ice-cold water. Crude product was collected by filtration, washed with 10percent NaHCO3 solution, dried and recrystallized from ethyl alcohol to get pure product 2. Data for 2: Yellow solid, yield: 82percent, mp: 125–127 °C; IR (KBr, cm 1): v3112 (N–H, broad), 3024 (C–H, aromatic), 2962 (C–H, aliphatic), 1680 (C55O), 1560 (C55C, aromatic); 1H NMR (300 MHz, DMSO-d6): δ 11.12 (s, 1H, NH), 7.85 (s, 1H, CH of indole ring), 7.62 (d, 1H, J = 2.0 Hz, Ar–H), 7.39 (dd, 2H, J = 2.0, 8.0 Hz, Ar–H), 7.37 (d, 1H, J = 8.0 Hz, Ar–H), 4.00 (q, 2H, OCH2), 3.45 (s, 2H, CH2CO), 1.24 (t, 3H, CH3); MS: m/z 203 (M+).
78%
for 3 h; Reflux
General procedure: Indol-3-acetic acid or 2-pyrazine carboxylic acid (5.5 mmol) were heated under reflux for 3 h in 90 mL ethanol and 15 mL concentrated H2SO4. The solution was neutralized with saturated Na2CO3 solution and filtered. The volume was reduced in vacuum and extracted with four 30 mL aliquots of dichloromethane. The combined fractions were washed with 10 mL of water and dried over anhydrous MgSO4. The dichloromethane was removed using vacuum to yield the ethyl carboxylate derivatives, 8a mp. 1–2 °C(Lit. 1–2 °C, Vlaovic et al., 1990) or 8b mp. 46–47 °C (Lit. 48–49 °C, Yoshino et al., 2006) which crystallized on cooling.
Reference：
[1] Journal of Heterocyclic Chemistry, 1986, vol. 23, p. 1777 - 1779
[2] Arzneimittel-Forschung/Drug Research, 2001, vol. 51, # 10, p. 814 - 824
[3] Patent: EP2548863, 2013, A1, . Location in patent: Paragraph 0247
[4] Patent: WO2013/10881, 2013, A1, . Location in patent: Page/Page column 95-96
[5] Chinese Chemical Letters, 2013, vol. 24, # 2, p. 127 - 130
[6] Organic Letters, 2017, vol. 19, # 9, p. 2274 - 2277
[7] Medicinal Chemistry Research, 2015, vol. 24, # 6, p. 2529 - 2550
[8] Journal of Medicinal Chemistry, 1999, vol. 42, # 4, p. 638 - 648
[9] European Journal of Medicinal Chemistry, 2012, vol. 55, p. 432 - 438
[10] Letters in Drug Design and Discovery, 2012, vol. 9, # 8, p. 780 - 788,9
[11] Tetrahedron Letters, 2015, vol. 56, # 8, p. 981 - 985
[12] Chemical Communications, 2018, vol. 54, # 65, p. 9083 - 9086
3
[ 87-51-4 ]
[ 778-82-5 ]
Yield
Reaction Conditions
Operation in experiment
90%
With sulfuric acid In ethanol; water
REFERENCE EXAMPLE 12 3-Ethoxycarbonylmethylindole A mixture of 5.0 g (28.5 mmols) of indole-3acetic acid, 250 ml of ethanol and 5 ml of conc. sulfuric acid was heated under reflux for 2 hours. After cooling to 0° C., the mixture was neutralized with a 2 normal aqueous sodium hydroxide solution. The solvent was evaporated under reduced pressure, and then water was added to the residue followed by extraction of the solution with chloroform. The chloroform layer was washed with an aqueous saturated sodium chloride solution and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was dried to afford 5.2 g (yield: 90percent) of the title compound. NMR (CDCl3) δ (ppm): 8.10(1H, brs), 7.0-7.7(4H, m), 6.97(1H, s), 4.15(2H, q, J=7.1 Hz), 3.73(2H, s), 1.23(3H, t, J=7.1 Hz)
Reference：
[1] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2002, vol. 41, # 12, p. 2647 - 2654
[2] Arzneimittel-Forschung/Drug Research, 2003, vol. 53, # 5, p. 301 - 306
10
[ 76367-43-6 ]
[ 59-88-1 ]
[ 778-82-5 ]
Reference：
[1] Journal of the American Chemical Society, 1951, vol. 73, p. 2756,2758
[2] Journal of the American Chemical Society, 1951, vol. 73, p. 5155
[3] Canadian Journal of Research, Section B: Chemical Sciences, 1935, vol. 13, p. 170,172
11
[ 18443-04-4 ]
[ 778-82-5 ]
Reference：
[1] Chemistry of Heterocyclic Compounds (New York, NY, United States), 1980, vol. 16, # 5, p. 501 - 506[2] Khimiya Geterotsiklicheskikh Soedinenii, 1980, # 5, p. 645 - 650
12
[ 771-51-7 ]
[ 778-82-5 ]
Reference：
[1] Chemistry of Heterocyclic Compounds (New York, NY, United States), 1980, vol. 16, # 5, p. 501 - 506[2] Khimiya Geterotsiklicheskikh Soedinenii, 1980, # 5, p. 645 - 650
13
[ 96296-38-7 ]
[ 111-46-6 ]
[ 778-82-5 ]
Reference：
[1] Canadian Journal of Chemistry, 1957, vol. 35, p. 1578,1580
With hydrazine hydrate; In ethanol; for 8h;Reflux;
Hydrazine hydrate (99%, 2 mL, 40 mmol) was added to a solution of compound 7 (2.03 g, 10 mmol) in dry ethanol (50 mL) and the resulting mixture was heated under reflux for 8 h. The reaction mixture was cooled to room temperature and the solid obtained was filtered off and washed with a small quantity of ethanol to give the desired intermediate 8. Yield: 1.80 g, 95%, white solid, mp 125-127 C. 1H NMR (600 MHz, DMSO-d6): d 3.46 (s, 2H), 4.20 (s, 2H), 6.98 (t, J 7.8 Hz, 1H), 7.07 (t, J 7.8 Hz, 1H), 7.18 (s, 1H), 7.34 (d,J 7.8 Hz, 1H), 7.58 (d, J 7.8 Hz, 1H), 9.16 (s, 1H), 10.87 (s, 1H). 13CNMR (150 MHz, DMSO-d6): d 30.8, 108.7, 111.3, 118.3, 118.7, 120.8,123.6, 127.2, 136.1, 170.3. EI-MS: m/z (%) 189 (M, 26), 144 (14), 130 (100), 77 (7).
90%
With hydrazine hydrate; In ethanol; for 6h;Reflux;
General procedure: A mixture of the ester derivative 8a or 8b (5.5 mmol) and hydrazine hydrate (11 mmol) in 50 mL of ethanol was heated under reflux for 6 h. The reaction mixture was left overnight at room temperature, and the solid which separated was collected by filtration. The solid was then washed with ethanol, dried, and recrystallized from ethanol (Yoshino et al., 2006; Vlaovic et al., 1990).
85%
With hydrazine hydrate; In ethanol; for 4h;Reflux;
General procedure: To a solution of indole carboxylic acid 2 (1 mmol) in ethanol (20 mL) was added catalytic amount of concentrated sulphuric acid (0.2 mL) and allowed to reflux for 20 h. After completion of the reaction, ethanol was removed and the residue was extracted with ethyl acetate (30 mL) and washed with saturated sodium bicarbonate solution (25 mL). Organic layer was dried over sodium sulphate and evaporated to give corresponding ester in good yields (85-95%). The solution of an appropriate ester (1 mmol) and hydrazine hydrate (2 mmol) in ethanol (15 mL) was refluxed for 4 h. Reaction mixture was cooled and the solid obtained was filtered and recrystallized from ethanol to obtain pure hydrazides 3aec, 3g and 3h. Yield 85%; Off-white solid, mp. 145-146 C. 1H NMR (400 MHz, CDCl3, delta ppm): delta 11.0 (s, 1H), 9.65 (s, 1H), 7.59 (dd, J = 7.8 Hz, J = 1.6 Hz, 1H), 7.30 (d, J = 7.8 Hz, 1H), 7.09 (d, J = 7.8 Hz, 1H), 6.98 (d, J = 7.8 Hz, 2H), 4.45 (s, 2H), 3.40 (s, 2H). IR (KBr, nu cm-1): 3317, 1649, 1623, 1235, 1063, 812. MS (ESI) m/z calcd for C10H11N3O (M + H)+ 190.1, obsd 190.1.
78%
With hydrazine hydrate; In ethanol; for 7h;Reflux;
a mixture of compound 2 (0.01 mol) and hydrazine hydrate (0.025 mol) in ethanol (20 mL) was refluxed for 7 h, cooled to room temperature and filtered. The crude product was recrystallized from ethanol to give the new intermediate 3. Data for 3: Pale yellow solid, yield: 78%, mp: 140-142 C; IR (KBr, cm 1): v3330-3200 (NHNH2), 3125 (N-H), 3012 (C-H, aromatic), 2945 (C-H, aliphatic), 1640 (C55O), 1545 (C55C, aromatic); 1H NMR (300 MHz, DMSO-d6): delta 11.35 (s, 1H, NH), 7.75 (s, 1H, CH of indole), 7.74 (d, 1H, J = 4.5 Hz, Ar-H), 7.42 (dd, 2H, J = 4.5, 7.5 Hz, Ar-H), 7.28 (d, 1H, J = 7.5 Hz, Ar-H), 7.70 (s, 1H, CONH), 5.30 (s, 2H, NH2), 3.58 (s, 2H, CH2); MS: m/z 189 (M+).
With hydrazine hydrate; at 80℃;
General procedure: At first several different acyl hydrazines B were synthesized. To do this, we have started with corresponding carboxylic acid A in solvent EtOH (2mL/mmol), 4 equivalents of thionyl chloride (SOCl2) was added drop wise at room temperature and refluxed with stirring for 5-12 h (monitored by TLC). SOCl2 and EtOH were evaporated. Water was added to the crude mixture, extracted with dichloromethane (DCM) and dried with anhydrous Na2SO4. DCM was evaporated and the residue was dried at high vacuum which provided the ethyl ester of the corresponding carboxylic acid A. The ester was added drop wise to hydrazine hydrate (NH2NH2.H2O) (5mmol/1mmol of ethyl carboxylate) and heated at 80 C for 5-20 h (monitored by TLC) and allowed to stand for 12 h. If solid appeared it was filtered off and the residue was dried in high vacuum at 80 C for 12 h. If solid was not obtained, the reaction mixture was freezed and again brought to the room temperature. Solid thus obtained was filtered off and the residue was dried in high vacuum at 80 C for 12 h that leads us different acyl hydrazine B corresponding to the starting carboxylic acid A.
Ethyl 1H-indol-3-ylacetate Indol-3-ylacetic acid (1.00 g, 5.71 mmol) was dissolved in 25 ml ethanol and concentrated sulphuric acid (1.0 ml, 18.4 mmol) was added. The mixture was stirred at reflux for 2 h and cooled to 0 ºC in an ice bath before neutralization with 2N sodium hydroxide solution. The organics were evaporated under reduced pressure and the mixture was partitioned between dichloromethane and water. The aqueous phase was extracted twice with dichloromethane and the combined organic were washed with brine, dried over sodium sulphate, filtered and evaporated under reduced pressure to give 1.02 g (5.02 mmol, 88%) of the title compound as a brown oil. Purity 100%.1H NMR (300 MHz, CHLOROFORM-d) delta ppm 8.09 (br. s., 1 H), 7.63 (d, J=7.69 Hz, 1 H), 7.35 (d, J=7.69 Hz, 1 H), 7.04 - 7.25 (m, 3 H), 4.17 (q, J=7.14 Hz, 2 H), 3.77 (s, 2 H), 1.26 (t, J=7.14 Hz, 3 H).UPLC/MS (3 min) retention time 1.58 min.LRMS: m/z 204 (M+1).
88%
lndol-3-ylacetic acid (1 .00 g, 5.71 mmol) was dissolved in 25 ml ethanol and concentrated sulphuric acid (1 .0 ml, 18.4 mmol) was added. The mixture was stirred at reflux for 2 h and cooled to 0 C in an ice bath before neutralization with 2N sodium hydroxide solution. The organics were evaporated under reduced pressure and the mixture was partitioned between dichloromethane and water. The aqueous phase was extracted twice with dichloromethane and the combined organic were washed with brine, dried over sodium sulphate, filtered and evaporated under reduced pressure to give 1 .02 g (5.02 mmol, 88%) of the title compound as a brown oil. Purity 100%. 1 H N MR (300 MHz, CHLOROFORM-d) delta ppm 8.09 (br. s., 1 H), 7.63 (d, J=7.69 Hz, 1 H), 7.35 (d, J=7.69 Hz, 1 H), 7.04 - 7.25 (m, 3 H), 4.17 (q, J=7.14 Hz, 2 H), 3.77 (s, 2 H), 1 .26 (t, J=7.14 Hz, 3 H). UPLC/MS (3 min) retention time 1 .58 min. LRMS: m/z 204 (M+1 ).
82%
With sulfuric acid; for 2h;Reflux;
To the solution of indole-3-acetic acid (1) (0.01 mol) in absolute ethyl alcohol (25 mL), conc. H2SO4 (2 mL) was added. The mixture was refluxed for 2 h. After completion of the reaction (monitored by TLC), the mixture was poured into ice-cold water. Crude product was collected by filtration, washed with 10% NaHCO3 solution, dried and recrystallized from ethyl alcohol to get pure product 2. Data for 2: Yellow solid, yield: 82%, mp: 125-127 C; IR (KBr, cm 1): v3112 (N-H, broad), 3024 (C-H, aromatic), 2962 (C-H, aliphatic), 1680 (C55O), 1560 (C55C, aromatic); 1H NMR (300 MHz, DMSO-d6): delta 11.12 (s, 1H, NH), 7.85 (s, 1H, CH of indole ring), 7.62 (d, 1H, J = 2.0 Hz, Ar-H), 7.39 (dd, 2H, J = 2.0, 8.0 Hz, Ar-H), 7.37 (d, 1H, J = 8.0 Hz, Ar-H), 4.00 (q, 2H, OCH2), 3.45 (s, 2H, CH2CO), 1.24 (t, 3H, CH3); MS: m/z 203 (M+).
78%
With sulfuric acid; for 3h;Reflux;
General procedure: Indol-3-acetic acid or 2-pyrazine carboxylic acid (5.5 mmol) were heated under reflux for 3 h in 90 mL ethanol and 15 mL concentrated H2SO4. The solution was neutralized with saturated Na2CO3 solution and filtered. The volume was reduced in vacuum and extracted with four 30 mL aliquots of dichloromethane. The combined fractions were washed with 10 mL of water and dried over anhydrous MgSO4. The dichloromethane was removed using vacuum to yield the ethyl carboxylate derivatives, 8a mp. 1-2 C(Lit. 1-2 C, Vlaovic et al., 1990) or 8b mp. 46-47 C (Lit. 48-49 C, Yoshino et al., 2006) which crystallized on cooling.
With sulfuric acid; for 20h;Reflux;
General procedure: To a solution of indole carboxylic acid 2 (1 mmol) in ethanol (20 mL) was added catalytic amount of concentrated sulphuric acid (0.2 mL) and allowed to reflux for 20 h. After completion of the reaction, ethanol was removed and the residue was extracted with ethyl acetate (30 mL) and washed with saturated sodium bicarbonate solution (25 mL). Organic layer was dried over sodium sulphate and evaporated to give corresponding ester in good yields (85-95%). The solution of an appropriate ester (1 mmol) and hydrazine hydrate (2 mmol) in ethanol (15 mL) was refluxed for 4 h. Reaction mixture was cooled and the solid obtained was filtered and recrystallized from ethanol to obtain pure hydrazides 3a-c, 3g and 3h.
With thionyl chloride;Reflux;
General procedure: At first several different acyl hydrazines B were synthesized. To do this, we have started with corresponding carboxylic acid A in solvent EtOH (2mL/mmol), 4 equivalents of thionyl chloride (SOCl2) was added drop wise at room temperature and refluxed with stirring for 5-12 h (monitored by TLC). SOCl2 and EtOH were evaporated. Water was added to the crude mixture, extracted with dichloromethane (DCM) and dried with anhydrous Na2SO4. DCM was evaporated and the residue was dried at high vacuum which provided the ethyl ester of the corresponding carboxylic acid A. The ester was added drop wise to hydrazine hydrate (NH2NH2.H2O) (5mmol/1mmol of ethyl carboxylate) and heated at 80 C for 5-20 h (monitored by TLC) and allowed to stand for 12 h. If solid appeared it was filtered off and the residue was dried in high vacuum at 80 C for 12 h. If solid was not obtained, the reaction mixture was freezed and again brought to the room temperature. Solid thus obtained was filtered off and the residue was dried in high vacuum at 80 C for 12 h that leads us different acyl hydrazine B corresponding to the starting carboxylic acid A.
With hydrogenchloride; borane pyridine; In ethanol; at 0 - 20℃; for 1h;
2.17 g of compound 1b was dissolved in 10 ml of a mixed solution of concentrated hydrochloric acid-ethanol (1:1), and slowly added with 5.0 equivalent of pyridinium-borane (BH3.Py) solution at 0 C. The reaction solution was warmed to room temperature, and stirred for 1 hour. The reaction solution was concentrated under reduced pressure. The residues were added with 60 ml of 10% sodium carbonate aqueous solution to adjust the pH to 8, and extracted with 80 ml of ethyl acetate for three times. The ethyl acetate layer was separated, and purified by column chromatography with petroleum ether: ethyl acetate 5:1 as the eluent to obtain the title compound 1c (0.87 g, yield: 40%).
With mercaptoacetic acid; lithium hydroxide; In N,N-dimethyl-formamide; at 20℃;Inert atmosphere;
General procedure: The N-tosyl indole or imidazole 66 (0.50 mmol) was dissolved in DMF (2 mL). Lithium hydroxide (48 mg, 2.00 mmol) was added followed by thioglycolic acid (30 mL, 0.60 mmol). The resulting solution was stirred at ambient temperature and the reaction progress monitored by TLC. Once reaction was complete (1.5-5 h), the solution was diluted with ethyl acetate (4 mL) and water (2 mL) and the layers separated. The aqueous layer was extracted with ethyl acetate (2×4 mL) and the combined organic solutions washed with saturated aqueous sodium carbonate (3×5 mL) then dried, filtered and evaporated to leave an essentially pure N-H indole or imidazole 67. Each product was identified by comparisons of mp and 1H NMR data with authentic material.
With N-Bromosuccinimide; In dichloromethane; at 0℃; for 3h;
To a solution of 15.0 g (73.8 mmol) of ethyl (indol-3-yl)acetate in 75 ml of anhydrous dichloromethane at 0 C. was added 13.1 g (73.8 mmol) of NBS in small portions. The mixture was stirred at 0 C. for 3 h and then quickly concentrated under reduced pressure (argon was used to normalize the pressure after concentration to avoid decomposition due to the product's instability). Column chromatography with 99:1 toluene/ethanol afforded 10.5 g (50%) of the 2-bromoindole as a yellow oil. [0281] 1H NMR (CDCl3) d 8.22 (s, 1H), 7.35 (d, J=8.5 Hz, 1H), 7.20 (d, J=7.5 Hz, 1H), 7.16 (m, 2H), 4.16 (q, J=7 Hz, 2H), 3.72 (s, 2H), 1.25 (t, J=7 Hz, 3H); MS 281 (M+).
With N-Bromosuccinimide; In dichloromethane; at 0 - 20℃; for 6h;
To a solution of ethyl 2-(lH-indol-3-yl)acetate (5 g, 24.6 mmol) in 25 ml of DCM was added N-bromosuccinimide (4.38 g, 24.6 mmol) in small portions at 0C. The mixture was warmed to room temperature and stirred for 6 hours. Di-ie/t-butyl pyrocarbonate (10.74 g, 49.2 mmol), DIPEA (8.6 ml, 49.5 mmol) and DMAP(cat) was added to the mixture. The reaction was stirred overnight. The mixture was diluted with DCM (100 ml) and washed with HC1 (0.5 N, 2 x 50ml). The organic layer was dried with Na2S04, filtered and concentrated. The crude product was introduced to a silica gel loading column and purified by column chromatography on silica (5-20 EtOAc/ hexanes) to get 6.3 g (16.5 mmol) of product. MS (m/z) 382 [M+H]+.
With triethylamine;dmap; In tetrahydrofuran; at 20℃; for 16h;
Ethyl 1H-indol-3-ylacetate (2 5 g, 12.3 MMOL) was dissolved in THF (60 mL) and to the resulting solution was added Di-tert-butyl carbonate (2. 9 g, 16. 6 MMOL), ET3N (1. 89 mL), and DMAP (150 mg, 1. 23 MMOL). The reaction was stirred for 16 h at rt. The solvent was removed under vacuum and the residue was re-dissolved in ET20 and saturated NAHC03 was added and the mixture was stirred vigorously for 30 min. The organic phase was collected, and dried over NA2SO4. The solvent was removed by vacuum. The crude product was purified further by passing it through a plug of silica using ET20 as eluent. The solvent was removed under vacuum to give ter-butyl 3-(2-ETHOXY-2-OXOETHYL)-1H-INDOLE-1- carboxylate as an oil (3. 73 g, 99%) :'H NMR (CDC13) 8 8. 14 (m, 1H), 7. 54 (m, 2H), 7. 32 (m, 1 H), 7. 24 (m, 2H), 4. 19 (q, 2H), 3. 71 (s, 1H), 1. 68 (s, 9H), 1. 29 (t, 3H).
With dmap; triethylamine; In dichloromethane; at 20℃; for 18h;
Starting Compounds; A1. tert-Butyl 3-(2-ethoxy-2-oxoethyl)-1 H-indole-1-carboxylate; Ethyl indole-3-acetate (107.6 g) is dissolved in dichloromethane (500 ml), di-tert-butyl dicarbonate (127.0 g), triethylamine (80.0 ml), and 4-dimethylaminopyridine (0.50 g) are added and the solution is stirred for 18 h at RT. After that, the solution is concentrated in vacuo. The crude product is purified by flash chromatography (silica gel, eluting with ethyl acetate / petroleum ether 1 :9 (v/v)) to yield the title compound as a light-yellow oil.MS (IVlNH4+ found) = 320.8
Preparation 13 Ethyl(2-Bromoindol-3-yl)acetate (X=H, n=1) To a solution of 15.0 g (73.8 mmol) of ethyl (indol-3-yl)acetate in 75 ml of anhydrous dichloromethane at 0 C. was added 13.1 g (73.8 mmol) of NBS in small portions. The mixture was stirred at 0 C. for 3 h and then quickly concentrated under reduced pressure (argon was used to normalize the pressure after concentration to avoid decomposition due to the product's instability). Column chromatography with 99:1 toluene/ethanol afforded 10.5 g (50%) of the 2-bromoindole as a yellow oil. 1H NMR (CDCl3) d 8.22 (s, 1H), 7.35 (d, J=8.5 Hz, 1H), 7.20 (d, J=7.5 Hz, 1H), 7.16 (m, 2H), 4.16 (q, J=7 Hz, 2H), 3.72 (s, 2H), 1.25 (t, J=7 Hz, 3H); MS 281 (M+).
[N-(n-butyl)-(indole-3-yl)]acetic acid ethyl ester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
68%
With NaH; In dimethyl sulfoxide;
[N-(n-butyl)-(indole-3-yl)]acetic acid ethyl ester A solution of 0.66 g (27.5 mMol) NaH in 200 ml DMSO is added under nitrogen atmosphere dropwise to a solution of 5.1 g commercially available (25 mMol) <strong>[778-82-5](indole-3-yl)acetic acid ethyl ester</strong> in 30 ml DMSO at room temperature. After 30 minutes 3.2 ml (27.6 mMol) n-butyliodide are added. The mixture is stirred for 3 hours, the reaction mixture is diluted with water and extracted with ether. After drying, the solvent is removed under reduced pressure and the residue is purified by column chromatography on silica gel. Eluding solvent: dichloromethane (petroleum ether (7:2, v/v). 4.4 g of a yellow oil are obtained. Yield: 68% of theory.
REFERENCE EXAMPLE 12 3-Ethoxycarbonylmethylindole A mixture of 5.0 g (28.5 mmols) of indole-3acetic acid, 250 ml of ethanol and 5 ml of conc. sulfuric acid was heated under reflux for 2 hours. After cooling to 0 C., the mixture was neutralized with a 2 normal aqueous sodium hydroxide solution. The solvent was evaporated under reduced pressure, and then water was added to the residue followed by extraction of the solution with chloroform. The chloroform layer was washed with an aqueous saturated sodium chloride solution and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was dried to afford 5.2 g (yield: 90%) of the title compound. NMR (CDCl3) delta (ppm): 8.10(1H, brs), 7.0-7.7(4H, m), 6.97(1H, s), 4.15(2H, q, J=7.1 Hz), 3.73(2H, s), 1.23(3H, t, J=7.1 Hz)
With dmap; triethylamine; at 20℃;Inert atmosphere;
General procedure: An N-H indole or imidazole 67 (2.00 mmol) was dissolved in triethylamine (30 mL) and tosyl chloride (2.20 mmol) and DMAP (?20 mg) were added. The resulting solution was stirred at ambient temperature overnight then poured into a mixture of water (50 mL) and dichloromethane (100 mL). The separated organic solution was washed with 2 M hydrochloric acid (2×50 mL) and water (50 mL) then dried filtered and evaporated. The residue was usually of sufficient purity to use directly after high vacuum drying. If this were not the case, crystallisation from methanol provided pure material, generally in >85% yields after crystallisation from (aq) methanol or EtOAc/petrol. Melting point data and literature references are given in Table 1.
To a solution of (1 H-indol-3-yl)-acetic acid ethyl ester (2.5 g, 12.30 mmol) in THF (58 mL) at 0C was added sodium hydride (60% in mineral oil, 0.354 g, 14.8 mmol) portionwise under argon. The dark brown solution was stirred at 0C for 45 min before dropwise addition of chlorosulfonylisocyanate (2.14 mL, 24.6 mmol). The reaction mixture was allowed to warm to RT overnight under stirring. Acetic acid (3 mL) was then added to the mixture which was stirred at RT for 20 min. Ice was added to mixture which was stirred for 60 min then diluted with water and extracted with EtOAc (3x). The combined organic extracts were washed with brine, dried (Phase separator) and concentrated in vacuo. The residual oil was purified via flash column chromatography on silica gel (EtOAc/cyclohexane 1 :3 to 2:3) to give the desired material. TLC, Rf (EtOAc/cyclohexane 1 :1) = 0.35; MS: 247 [M+H]+, 493 [2M+H]+; tR (HPLC conditions b) 3.51 min.
With copper(I) oxide; salicylaldehyde-oxime; caesium carbonate; In acetonitrile; at 120℃; for 24h;Inert atmosphere; Microwave irradiation;
Ethyl {1-[2-[(cyclopropylcarbonyl)(ethyl)amino]methyl}-4-(trifluoromethyl)phenyl]-1H-indol-3-yl}acetate 4 (150 mg, 0.43 mmol) and the title compound of Preparation 92 (130 mg, 0.64 mmol) were dissolved in 2 ml acetonitrile. Salicylaldoxime (3 mg, 0.02 mmol), caesium carbonate (314 mg, 0.96 mmol) and copper(I) oxide (4 mg, 0.03 mmol) were added under argon atmosphere. The mixture was heated in the microwave for 4 h at 120 C. Further salicylaldoxime (8 mg, 0.06 mmol), copper(I) oxide (6 mg, 0.04 mmol) and acetonitrile (0.5 ml) were added and the mixture was heated in the microwave for 20 h at 120 ºC. The mixture was filtered through Celite, washed with ethyl acetate and evaporated under reduced pressure. The residue was partially purified using the Isolera Purification System (ether-hexane gradient, 0:100 rising to 100:0, then ethanol-ether gradient, 0-100 rising to 100:0) to give 21 mg of the crude title compound. Purity 83%.UPLC/MS (3 min) retention time 2.12 min.LRMS: m/z 473 (M+1).
With copper(I) oxide; salicylaldehyde-oxime; caesium carbonate; In acetonitrile; at 120℃; for 24h;Microwave irradiation; Inert atmosphere;
The title compound of Preparation 4 (150 mg, 0.43 mmol) and the title compound of Preparation 92 (130 mg, 0.64 mmol) were dissolved in 2 ml acetonitrile. Salicylaldoxime (3 mg, 0.02 mmol), caesium carbonate (314 mg, 0.96 mmol) and copper(l) oxide (4 mg, 0.03 mmol) were added under argon atmosphere. The mixture was heated in the microwave for 4 h at 120 C. Further salicylaldoxime (8 mg, 0.06 mmol), copper(l) oxide (6 mg, 0.04 mmol) and acetonitrile (0.5 ml) were added and the mixture was heated in the microwave for 20 h at 120 C. The mixture was filtered through Celite, washed with ethyl acetate and evaporated under reduced pressure. The residue was partially purified using the Isolera Purification System (ether-hexane gradient, 0: 100 rising to 100:0, then ethanol-ether gradient, 0-100 rising to 100:0) to give 21 mg of the crude title compound. Purity 83%. UPLC/MS (3 min) retention time 2.12 min. LRMS: m/z 473 (M+1 ).
N,N'-(5,5'-(cyclohexane-1,3-diyl)bis(1,3,4-thiadiazole-5,2-diyl))bis(2-(1H-indol-3-yl)acetamide)[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With potassium tert-butylate; In N,N-dimethyl-formamide; at 120 - 140℃;Microwave irradiation;
A mixture of compound (1-31) (1 equivalent), the corresponding ester (2.5 equivalents), t-BuOK (3.0 equivalents) in DMF was stirred at 120-140 C for 30-60 min in a microwave oven. The resulting mixture was purified by standard methods to afford the desired products.
With caesium carbonate; In acetone; at 65℃; for 6h;Sealed tube;
Step 1. A mixture of ethyl 2-(lH-indol-3-yl)acetate (500 mg, 2.46 mmol), cesium carbonate (1.04 g, 3.20 mmol) and ethyl 2-bromoacetate (0.33 mL, 3.0 mmol) in acetone (20 mL) was sealed and heated in an oil bath at 65C for 6 h. The reaction mixture was filtered and the filtrate was concentrated in vacuo. The residual oil was taken up into DMF and then purified by preparative HPLC to afford the title compound diethyl 2,2'-(lH-indole-l,3- diyl)diacetate (255 mg) as an off-white solid. LC-MS retention time = 1.23 min; m/z = 290.3 [M+H]+. (Column: Waters Aquity BEH C18 2.1 X 50 mm 1.7^m-particles; Solvent A = 100% Water/ 0.05% TFA; Solvent B = 100% Acetonitrile/0.05% TFA; Flow Rate = 0.8 mL/min. Start % B = 2; Final % B = 98; Gradient Time = 1.5 minutes; Wavelength = 220 nm). NMR (400 MHZ, CDCh) delta ppm 7.65 (d, J=8.0 Hz, 1H), 7.32 - 7.22 (m, 3H), 7.21 - 7.11 (m, 2H), 4.83 (s, 2H), 4.21 (dq, J=19.0, 7.1 Hz, 4H), 3.80 (d, J=0.8 Hz, 2H), 1.29 (t, J=7.2 Hz, 6H).
1-[imino(4-methylpiperazin-1-yl)methyl]guanidine dihydrochloride[ No CAS ]
4-((1H-indol-3-yl)methyl)-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
22%
With sodium; In methanol;Reflux;
General procedure: Sodium (10 mmol) was dissolved in 10 mL of absolute methanol, then 4-methylpiperazin-1-yl biguanidine x 2HCl (5 mmol) and the appropriate carboxylic acidester 2e-19e (5 mmol) were added. The reaction mixture was refluxed for 15-30h. After cooling to room temperature, water (10 mL) was added and themixture was stirred for 0.5 h. The precipitated triazine product (2-19) was separated and crystallized from methanol.
With oxygen; ozone; In water; acetone; at 0℃; for 0.000555556h;
Experimental procedure :( Continues process) Example 4: Synthesis of Ethyl 4-oxo-l,4-dihydroquinoline-3-carboxylate (2): (0092) Indole-3-acetic acid ester 1(3 g, 14.77 mmol) was dissolved in acetone: water (50 mL, 2: 1), and loaded in syringe. Pump is used to pump this solution in syringe to a Tee junction where other inlet of Tee junction was connected to ozone generator where stream of 03 was passed to the Tee junction at 0 C. Outlet of Tee junction was connected to the continuous flow reactor where reaction takes place. Outlet of the flow reactor is connected to 2-neck round bottom flask. Flow rate of substrate 1(1.0 mL/min) and O3/O2(1000 mL/min) gas was kept to have 2 sec residence time for overall reaction. One neck is used to evacuate excesses 03 for quenchingand from other neck product was transferred to the other round bottom flask under stirring where water (0.1 mL/min) and ethyl acetate (1.0 niL) was pumped. The mixed solution was then pumped to the separating funnel for layer separation. Ethylacetate layer was then pumped(0.4 mL/min) to another Tee junction where other inlet of Tee junction was connected to the syringe filled with DMF-DMA in ethylacetate (0.4mL/min; 10% v/v). Outlet of Tee connected to the continuous flow reactor to maintain the 40 min residence time.Reaction mass, collected from at the outlet of the flow reactor, was evaporated to give dark brown syrup. This crude material was added dropwise into cold H20 (75 mL) under stirring. The precipitates thus formed were filtered, washed with H20 (50 mL), dried to give off-white solid (yield: 1.56 g; 54%)
With tetrabutyl-ammonium chloride; bis-[(trifluoroacetoxy)iodo]benzene; In dichloromethane; at -10℃;Green chemistry;
Add the starting material 11 (40 mg, 0.2 mmol), tetrabutylammonium chloride hydrate (67 mg,0.24 mmol)to the same reactor, then add 1.5 mL of the solvent dichloromethane, and control the reaction temperature to -10 C. A0.5 mL solution of[bis(trifluoroacetoxy)iodo]benzene (103 mg, 0.24 mmol) in dichloromethane was added dropwise, and the reaction was quickly confirmed by TLC.Thereaction was quenched by theaddition of 10 mLEtOAc EtOAc. Chromatography (petroleum ether / ethyl acetate, 3:1) gave 3-ethyl acetate 1-hydrogen-oxindole, 39.1 mg, yield 89%.
ethyl 2-[2-(4-chlorobenzoyl)-1H-indol-3-yl]acetate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
67%
With tin(IV) chloride; In dichloromethane; at -3 - 20℃;
General procedure: Tin(IV) chloride,7.8 g (30 mmol), was added dropwise to a solution of 2.0 g (10 mmol) of ester 1 and 12 mmol of the corresponding carboxylic acid chloride in 16 mL of anhydrous methylene chloride, maintaining the temperature not higher than -3 C. The mixture was stirred for 1 h at that temperature, allowed to slowly warm up to room temperature, and left overnight. It was then poured into a mixture of 50 g of crushed ice and 15 mL of aqueous HCl, stirred, and extracted with methylene chloride (4 × 25 mL). The combined extracts were washed in succession with 20 mL of water, 20 mL of a 5% aqueous solution of sodium hydrogen carbonate, and 20 mL of water again, dried over sodium sulfate, and evaporated under reduced pressure, and the residue was recrystallized from propan-2-ol and dried in air. Ethyl 2-[2-(4-chlorobenzoyl)-1H-indol-3-yl]-acetate (2a). Yield 67%, mp 147-148 C. 1H NMR spectrum (DMSO-d6), delta, ppm: 1.21 t (3H, OCH2CH3, J = 8.0 Hz), 3.82 s (2H, CH2), 4.04 q (2H, OCH2CH3, J = 8.0 Hz), 7.05 t (1H, 5-H, J = 8.0 Hz), 7.25 t (1H, 6-H, J = 8.0 Hz), 7.45 d (1H, 7-H, J = 8.0 Hz), 7.52 d (2H, 3?-H, 5?-H, J = 8.0 Hz), 7.56 d (1H, 4-H, J = 8.0 Hz), 7.78 d (2H, 2?-H, 6?-H, J = 8.0 Hz), 11.55 s (1H, NH). Mass spectrum: m/z 342 [M + 1]+. Found,%: C 66.80; H 4.73; N 4.12. C19H16ClNO3. Calculated,%: C 66.77; H 4.72; N 4.10. M 341.79.
ethyl 2-[2-(4-methylbenzoyl)-1H-indol-3-yl]acetate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
88%
With tin(IV) chloride; In dichloromethane; at -3 - 20℃;
General procedure: Tin(IV) chloride,7.8 g (30 mmol), was added dropwise to a solution of 2.0 g (10 mmol) of ester 1 and 12 mmol of the corresponding carboxylic acid chloride in 16 mL of anhydrous methylene chloride, maintaining the temperature not higher than -3 C. The mixture was stirred for 1 h at that temperature, allowed to slowly warm up to room temperature, and left overnight. It was then poured into a mixture of 50 g of crushed ice and 15 mL of aqueous HCl, stirred, and extracted with methylene chloride (4 × 25 mL). The combined extracts were washed in succession with 20 mL of water, 20 mL of a 5% aqueous solution of sodium hydrogen carbonate, and 20 mL of water again, dried over sodium sulfate, and evaporated under reduced pressure, and the residue was recrystallized from propan-2-ol and dried in air. Ethyl 2-[2-(4-methylbenzoyl)-1H-indol-3-yl]-acetate (2b). Yield 88%, mp 133-134 C. 1H NMR spectrum (DMSO-d6), delta, ppm: 1.20 t (3H, OCH2CH3, J = 8.0 Hz), 2.47 s (3H, 4?-CH3), 3.78 s (2H, CH2), 4.04 q (2H, OCH2CH3, J = 8.0 Hz), 7.04 t (1H, 5-H, J = 8.0 Hz,), 7.23 t (1H, 6-H, J = 8.0 Hz), 7.31 d (2H,3?-H, 5?-H, J = 8.0 Hz), 7.46 d (1H, 7-H, J = 8.0 Hz) 7.54 d (1H, 4-H, J = 8.0 Hz), 7.69 d (2H, 2?-H, 6?-H, J = 8.0 Hz), 11.51 s (1H, NH). Mass spectrum: m/z 322.2 [M + 1]+. Found, %: C 74.74; H 5.98; N 4.39. C20H19NO3. Calculated, %: C 74.75; H 5.96; N 4.36. M 321.36.
ethyl 2-[2-(3-methoxybenzoyl)-1H-indol-3-yl]acetate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
59%
With tin(IV) chloride; In dichloromethane; at -3 - 20℃;
General procedure: Tin(IV) chloride,7.8 g (30 mmol), was added dropwise to a solution of 2.0 g (10 mmol) of ester 1 and 12 mmol of the corresponding carboxylic acid chloride in 16 mL of anhydrous methylene chloride, maintaining the temperature not higher than -3 C. The mixture was stirred for 1 h at that temperature, allowed to slowly warm up to room temperature, and left overnight. It was then poured into a mixture of 50 g of crushed ice and 15 mL of aqueous HCl, stirred, and extracted with methylene chloride (4 × 25 mL). The combined extracts were washed in succession with 20 mL of water, 20 mL of a 5% aqueous solution of sodium hydrogen carbonate, and 20 mL of water again, dried over sodium sulfate, and evaporated under reduced pressure, and the residue was recrystallized from propan-2-ol and dried in air. Ethyl 2-[2-(3-methoxybenzoyl)-1H-indol-3-yl]-acetate (2c). Yield 59%, mp 88-89 C. 1H NMR spectrum(DMSO-d6), delta, ppm: 1.21 t (3H, OCH2CH3, J = 8.0 Hz), 3.79 s (2H, CH2), 3.85 s (3H, 3?-OCH3), 4.04 q (2H, OCH2CH3, J = 8.0 Hz), 7.04 t (1H, 5-H,J = 8.0 Hz), 7.13 d (1H, 4?-H, J = 8.0 Hz), 7.24 t (1H, 6-H, J = 8.0 Hz), 7.26 s (1H, 2?-H) 7.33 d (1H, 6?-H,J = 8.0 Hz), 7.41 t (1H, 5?-H, J = 8.0 Hz), 7.47 d (1H,7-H, J = 8.0 Hz), 7.54 d (1H, 4-H, J = 8.0 Hz), 11.55 s (1H, NH). Mass spectrum: m/z 338.2 [M + 1]+. Found,%: C 71.17; H 5.65; N 4.12. C20H19NO4. Calculated,%: C 71.20; H 5.68; N 4.15. M 337.37.
ethyl 2-[2-(thiophen-2-ylcarbonyl)-1H-indol-3-yl]acetate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
76%
With tin(IV) chloride; In dichloromethane; at -3 - 20℃;
General procedure: Tin(IV) chloride,7.8 g (30 mmol), was added dropwise to a solution of 2.0 g (10 mmol) of ester 1 and 12 mmol of the corresponding carboxylic acid chloride in 16 mL of anhydrous methylene chloride, maintaining the temperature not higher than -3 C. The mixture was stirred for 1 h at that temperature, allowed to slowly warm up to room temperature, and left overnight. It was then poured into a mixture of 50 g of crushed ice and 15 mL of aqueous HCl, stirred, and extracted with methylene chloride (4 × 25 mL). The combined extracts were washed in succession with 20 mL of water, 20 mL of a 5% aqueous solution of sodium hydrogen carbonate, and 20 mL of water again, dried over sodium sulfate, and evaporated under reduced pressure, and the residue was recrystallized from propan-2-ol and dried in air. Ethyl 2-[2-(thiophen-2-ylcarbonyl)-1H-indol-3-yl]acetate (2g). Yield 76%, mp 122-123 C. 1H NMR spectrum (DMSO-d6), delta, ppm: 1.23 t (3H, OCH2CH3, J = 8.0 Hz), 3.98 s (2H, CH2), 4.08 q (2H, OCH2CH3,J = 8.0 Hz), 7.06 t (1H, 5-H, J = 8.0 Hz), 7.22-7.26 m (2H, 6-H, 4?-H), 7.48 d (1H, 7-H, J = 8.0 Hz), 7.56 d (1H, 4-H, J = 8.0 Hz) 7.85 d (1H, 5?-H, J = 4.0 Hz), 7.87 d (1H, 3?-H, J = 4.0 Hz), 11.58 s (1H, NH). Mass spectrum: m/z 314.0 [M + 1]+. Found, %: C 65.14;H 4.83; N 4.49. C17H15NO3S. Calculated, %: C 65.16;H 4.82; N 4.47. M 313.37.
With sodium hydride; In tetrahydrofuran; mineral oil; for 16h;Inert atmosphere; Reflux;
Nitrile 30 (57 mg, 0.241 mmol), sodium azide(47.1 mg), and triethylammonium chloride (99.7 mg) were suspended in dry toluene (1 mL) in anatmosphere of nitrogen. The suspension was stirred at reflux for 3 days. The reaction was cooledto room temperature and water was added. The aqueous phase was collected and acidified withconcentrated hydrochloric acid. Upon acidification, the compound in question precipitated as ano-white solid which was collected by vacuum filtration (50.2 mg, 75%); mp 184-185 C. H (400 MHz,DMSO-d6) 7.98 (1H, s, ArH), 7.90 (1H, s, ArH), 7.67 (1H, d, J = 8.4 Hz, ArH), 7.42 (1H, d, J = 8.0 Hz,ArH), 4.39 (2H, s, CH2). C (100 MHz, DMSO-d6) 155.5 (Cq), 144.9, 126.9 (Cq), 126.4, 121.8, 117.7 (Cq),115.3 (Cq), 115.2, 18.3 (CH2). One quaternary carbon was not observed. LRMS (ESI): m/z 279.0 [M (79Br)+ H]+, 280.9 [M (81Br) + H]+. HRMS (ESI): 276.9758 [M (79Br) H], 278.9738 [M (81Br) H].
ethyl 2-(2-benzoyl-1H-indol-3-yl)acetate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
77%
With zinc(II) chloride; In dichloromethane; for 6h;Reflux;
A mixture of 10 g (49.26 mmol) of compound 1, 7 mL (60.24 mmol) of benzoyl chloride, and 18 g(132.35 mmol) of zinc(II) chloride in 30 mL of anhydrous methylene chloride was refluxed with stirring for6 h. The mixture was cooled, and a solution of 21.7 g(264.71 mmol) of sodium acetate in 60 mL of waterwas added with stirring. Methylene chloride was distilled off from the mixture on heating with stirring,the residue was cooled to room temperature, and the brown crystals were filtered off, washed with water,dried, and recrystallized from methanol. Yield 11.6 g(77%), fine colorless crystals, mp 129-130C. 1H NMRspectrum, delta, ppm: 1.18 t (3H, CH3, J = 7.2 Hz), 3.87 s(2H, CH2), 4.05 q (2H, CH2, J = 6.8 Hz), 7.11 t (1H,Harom, J = 7.6 Hz), 7.31 t (1H, Harom, J = 7.6 Hz),7.51 d (1H, Harom, J = 8.0 Hz), 7.57 t (2H, Harom, J =7.2 Hz), 7.67 t (2H, Harom, J = 7.2 Hz), 7.78 d (2H,Harom, J = 7.2 Hz), 11.65 s (1H, NH). 13C NMR spectrum,deltaC, ppm: 13.9 (CH3), 30.4 (CH2), 59.9 (CH2),112.6, 115.0, 119.8, 120.3, 125.0, 127.4, 128.3 (2C),128.6 (2C), 131.8, 131.9, 136.5, 138.7, 170.3 (COOEt),189.0 (COPh). Found, %: C 74.31; H 5.60; N 4.58;O 15.51. C19H17NO3. Calculated, %: C 74.25; H 5.58;N 4.56; O 15.62.
2.0 g of indoleacetic acid was dissolved in 20 ml of DMF, and then K2CO3 (1.2 equivalent) was added thereto. The resulting mixture was stirred at room temperature for 30 minutes, and then added slowly with EtBr (1.2 equivalent) dropwise. After completion of the addition, the reaction mixture was stirred and refluxed for 4 hours. The reaction solution was then filtered. The filtrate was concentrated under reduced pressure. The residues were purified by column chromatography with petroleum ether: ethyl acetate 5:1 as the eluent to obtain the compound 1b (2.17 g, yield: 94%).
2-(4-(allylamino)phenyl)-2-(1H-indol-3-yl)ethanoic acid ethyl ester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
76%
With hydrogenchloride; aluminum (III) chloride In ethanol; water at 80℃;
Example 15: 2-(4-(allylamino)phenyl)-2-(1H-indol-3-yl)ethyl acetate
In a 5ml flask, 77mg (0.25mmol) 2-(1H-indol-3-yl)-2-(p-tolylamino) ethyl acetate was dissolved in 2mL ethanol, and then 67mg (0.50mmol) N, N-allyl aniline, 168 μl (0.5 mmol) 3M HCl, 13.3 mg (0.1 mmol) aluminum trichloride, and react under reflux at 80°C.Then the solvent ethanol was evaporated under reduced pressure, extracted with dichloromethane/water, dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, column chromatography (petroleum ether/ethyl acetate=3:1) to obtain 63mg of product, the yield was 76% .
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