* 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 N-Bromosuccinimide; dibenzoyl peroxide In tetrachloromethane for 1.5 h; Heating / reflux
Synthesis of 3-bromo-indan-1-one; 390 g (2.2 mol) N-bromosuccinimde (powder with no lumps) and 0.5 g benzoyl peroxide were added to 264 g indan-1-one in 1500 mL CCl4 and refluxed with mechanical stirring for 1.5 hours. The colour of the reaction mixture suddenly changed to yellow and all N-bromosuccinimde (heavier than CCl4) was converted to succinimide (lighter than CCl4). The reaction mixture was cooled to 20° C., filtered and concentrated in vacuo. Crude 3-bromo-indan-1-one was dissolved in 600 mL ethyl acetate/heptane (1:2), cooled 2 hours on an ice bath and then left in a freezer over night to give 257 g crystals of 3-bromo-indan-1-one (62percent yield).
51%
With N-Bromosuccinimide; dibenzoyl peroxide In tetrachloromethane for 1 h; Inert atmosphere; Reflux
3-Bromo-2,3-dihydro-lH-inden-l-one was generated as described by Treibs and Schroth 34. 2,3-Dihydro- lH-indan-1-one (528 mg, 4 mmol), N-bromosuccinimide (684 mg, 4 mmol) and benzoyl peroxide (30 mg, 0.12 mmol) were dissolved in CCl4 (10 mL) and heated to reflux for Ih under an N2 atmosphere. After cooling, succinimide was removed by filtration and the filtrate concentrated under high vacuum to yield the title compound as a straw-colored oil of >; 99percent purity as seen by GC-MS and NMR that was used without further purification (428 mg, 51percent yield). 1H NMR (600 MHz, CDCl3): δ 3.064 (dd, IH, /=19.7, /=2.3 Hz, CH2), 3.370 (dd, IH, /=19.7Hz, /=7.2Hz, CH2) 5.609 (dd, IH, /=7.2Hz, /=2.6Hz, C3-H), 7.468-7.520 (m, IH), 7.702-7.775 (m, 3H); 13C NMR (150 MHz, CDCl3): δ 40.28, 50.30, 127.29, 128.81, 128.86, 133.72, 138.00, 204.55; MS (EI) m/z (relative intensity): 208 ([77Br]M+', 22). CAS Registry No: [40774-41-2].
50%
With N-Bromosuccinimide; dibenzoyl peroxide In tetrachloromethane for 2 h; Reflux
To a solution of indan-1-one (5.00 g, 37.83 mmol) in carbon tetrachloride (25 mL), was added N-bromosuccinimide (7.41 g, 41.61 mmol) and a catalytic quantity of benzoyl peroxide. The reaction was refluxed for 2 h, after which time the reaction mixture was cooled and partitioned between diethyl ether and water. Purification by flash column chromatography on silica gel (eluant; petroleum ether:ethyl acetate, 9:1) afforded the title compound (2), a yellow oil (4.00g, 50percent) with the following physical properties: IR (DCM, υ) 1543, 1717, 2010, 2157 cm-1; 1HNMR (CDCl3, 400MHz) δppm = 3.06 (dd, J1= 19.8 Hz, J2= 2.3 Hz, 1H, CH2), 3.37 (dd, J1=19.8 Hz, J2=7.2 Hz, 1H, CH2), 5.61 (dd, J1=7.0 Hz, J2=2.1 Hz, 1H, CHBr), 7.49 (dt, J1=7.8 Hz, J2=4.0 Hz, 1H, Ar-H), 7.74 (m, 3 x Ar-H).
11 g
With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) In chloroform for 3 h; Inert atmosphere; Reflux
1-Indanone (8) (10 g, 0.0758 mol, 1.0 eq) react with N-bromosuccinimide (NBS) (13.8 g, 0.0758 mol 1.0 eq) in a catalyst azobisisobutyronitrile (AIBN), was refluxed in CHCl3 (100 mL) solvent for 3 h. After completion of reaction the reaction mixture was quenched with water, extracted with CHCl3, washed with water, dried over sodium sulphate and concentrated under reduced pressure to obtain the 11 g compound 9. 1H NMR (400 MHz, CDCl3); δ 7.70 (dd, 3H, Ar-H), 7.47 (m, 1H, Ar-H), 5.59 (q, 1H, CH-Br), 3.34 (dd, 2H, CH2-CO), 3.03 (dd, 1H, CH2-CO). Mass: m/z calcd. 211, found m/z 212 (M+1)+. HPLC purity (percent): 98.58.
Reference：
[1] Tetrahedron, 1995, vol. 51, # 32, p. 8953 - 8958
[2] Indian journal of chemistry, 1981, vol. 20 B, # 4, p. 303 - 307
[3] Patent: US2008/58329, 2008, A1, . Location in patent: Page/Page column 13
[4] Tetrahedron Letters, 2006, vol. 47, # 7, p. 1097 - 1099
[5] Tetrahedron, 2009, vol. 65, # 22, p. 4429 - 4439
[6] Patent: WO2010/108058, 2010, A2, . Location in patent: Page/Page column 25
[7] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 4, p. 1191 - 1194
[8] Journal of the American Chemical Society, 2005, vol. 127, # 30, p. 10482 - 10483
[9] Journal of the American Chemical Society, 1954, vol. 76, p. 5435
[10] Justus Liebigs Annalen der Chemie, 1961, vol. 639, p. 204 - 213
[11] Tetrahedron Asymmetry, 2003, vol. 14, # 4, p. 481 - 487
[12] Patent: US2002/13356, 2002, A1,
[13] European Journal of Medicinal Chemistry, 2010, vol. 45, # 1, p. 25 - 37
[14] Asian Journal of Chemistry, 2017, vol. 29, # 6, p. 1357 - 1359
[15] Organic Letters, 2017, vol. 19, # 24, p. 6692 - 6695
2
[ 83-33-0 ]
[ 480-90-0 ]
[ 40774-41-2 ]
Reference：
[1] Journal of Organic Chemistry, 2014, vol. 79, # 1, p. 223 - 229
3
[ 83-33-0 ]
[ 40774-41-2 ]
[ 1775-27-5 ]
Reference：
[1] European Journal of Pharmaceutical Sciences, 2005, vol. 24, # 4, p. 315 - 323
[2] Tetrahedron, 2009, vol. 65, # 22, p. 4429 - 4439
b) Inden-1-one <strong>[40774-41-2]3-Bromoindan-1-one</strong> (1.5) was dissolved in diethyl ether (10 ml). The temperature was kept at +2-+4 while TEA (2.7 ml) was added. The resulting mixture was further stirred at +2-+4 for 2 hours. The precipitated salt was filtered off and the filtrate evaporated. The crude inden-1-one was used for further reaction without purification. Yield was 0.9 g. 1H NMR (d6-DMSO): 5.99 (1H, d, J=6.0 Hz), 7.24 (1H, m), 7.28 (I H, m), 7.38 (1H, m), 7.45 (1H, m), 7.89 (1H, d, J=6.0 Hz).
With triethylamine; In tetrahydrofuran; at 0 - 20℃; for 1h;
Synthesis of 3-(7-fluoro-1H-indol-3-yl)-indan-1-one (Method 1); Triethylamine (4.5 mL; 32 mmol; 1.2 equiv.) was added to <strong>[40774-41-2]3-bromo-indan-1-one</strong> (5.6 g; 27 mmol) in 100 mL THF at 0 C. and stirred 1 h at r.t. The reaction mixture was filtered to remove triethylammonium bromide and concentrated in vacuo to give inden-1-one. 7-Fluoroindole (3.3 g, 22 mmol ) and Sc(OTf)3 (550mg, 5 mol %) were added to inden-1-one in 100 mL CH2Cl2 at 0 C. The reaction mixture was allowed to warm to room temperature over night. 100 mL ethyl acetate was added and the mixture was filtered through a silica gel plug and concentrated in vacuo. After flash chromatography (heptane/ethyl acetate, silica gel) 5.9 g 3-(7-fluoro-1H-indol-3-yl)-indan-1-one (82%) was isolated.
With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; for 1.5h;Heating / reflux;
Synthesis of 3-bromo-indan-1-one; 390 g (2.2 mol) N-bromosuccinimde (powder with no lumps) and 0.5 g benzoyl peroxide were added to 264 g indan-1-one in 1500 mL CCl4 and refluxed with mechanical stirring for 1.5 hours. The colour of the reaction mixture suddenly changed to yellow and all N-bromosuccinimde (heavier than CCl4) was converted to succinimide (lighter than CCl4). The reaction mixture was cooled to 20 C., filtered and concentrated in vacuo. Crude 3-bromo-indan-1-one was dissolved in 600 mL ethyl acetate/heptane (1:2), cooled 2 hours on an ice bath and then left in a freezer over night to give 257 g crystals of 3-bromo-indan-1-one (62% yield).
51%
With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; for 1h;Inert atmosphere; Reflux;
3-Bromo-2,3-dihydro-lH-inden-l-one was generated as described by Treibs and Schroth 34. 2,3-Dihydro- lH-indan-1-one (528 mg, 4 mmol), N-bromosuccinimide (684 mg, 4 mmol) and benzoyl peroxide (30 mg, 0.12 mmol) were dissolved in CCl4 (10 mL) and heated to reflux for Ih under an N2 atmosphere. After cooling, succinimide was removed by filtration and the filtrate concentrated under high vacuum to yield the title compound as a straw-colored oil of >; 99% purity as seen by GC-MS and NMR that was used without further purification (428 mg, 51% yield). 1H NMR (600 MHz, CDCl3): delta 3.064 (dd, IH, /=19.7, /=2.3 Hz, CH2), 3.370 (dd, IH, /=19.7Hz, /=7.2Hz, CH2) 5.609 (dd, IH, /=7.2Hz, /=2.6Hz, C3-H), 7.468-7.520 (m, IH), 7.702-7.775 (m, 3H); 13C NMR (150 MHz, CDCl3): delta 40.28, 50.30, 127.29, 128.81, 128.86, 133.72, 138.00, 204.55; MS (EI) m/z (relative intensity): 208 ([77Br]M+', 22). CAS Registry No: [40774-41-2].
50%
With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; for 2h;Reflux;
To a solution of indan-1-one (5.00 g, 37.83 mmol) in carbon tetrachloride (25 mL), was added N-bromosuccinimide (7.41 g, 41.61 mmol) and a catalytic quantity of benzoyl peroxide. The reaction was refluxed for 2 h, after which time the reaction mixture was cooled and partitioned between diethyl ether and water. Purification by flash column chromatography on silica gel (eluant; petroleum ether:ethyl acetate, 9:1) afforded the title compound (2), a yellow oil (4.00g, 50%) with the following physical properties: IR (DCM, upsilon) 1543, 1717, 2010, 2157 cm-1; 1HNMR (CDCl3, 400MHz) deltappm = 3.06 (dd, J1= 19.8 Hz, J2= 2.3 Hz, 1H, CH2), 3.37 (dd, J1=19.8 Hz, J2=7.2 Hz, 1H, CH2), 5.61 (dd, J1=7.0 Hz, J2=2.1 Hz, 1H, CHBr), 7.49 (dt, J1=7.8 Hz, J2=4.0 Hz, 1H, Ar-H), 7.74 (m, 3 x Ar-H).
With N-Bromosuccinimide;azobisisobutyronitrile;
a) 3-Bromoindan-1-one 1-Indanone (1 g) and NBS (1.4 g) was mixed with dry CC04 (20 ml). A catalytic amount of AIBN was added and the mixture was refluxed for 30 minutes and excited with light using 250 W lamp. The mixture was cooled in an ice bath and filtered. The filtrate was concentrated in an evaporator and used without further purification for the next step. Yield was 1.5 g. 1H NMR (d6-DMSO): 2.95 (1H, dd, J=19.6 Hz and 2.1 Hz), 3.51 (1H, dd, J=19.6 Hz and 7.0 Hz), 5.94 (1H, dd, J=7.0 Hz and 2.1 Hz), 7.58 (1H, m), 7.69 (1H, m), 7.77 (1H, m), 7.81 (1H, m).
11 g
With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In chloroform; for 3h;Inert atmosphere; Reflux;
1-Indanone (8) (10 g, 0.0758 mol, 1.0 eq) react with N-bromosuccinimide (NBS) (13.8 g, 0.0758 mol 1.0 eq) in a catalyst azobisisobutyronitrile (AIBN), was refluxed in CHCl3 (100 mL) solvent for 3 h. After completion of reaction the reaction mixture was quenched with water, extracted with CHCl3, washed with water, dried over sodium sulphate and concentrated under reduced pressure to obtain the 11 g compound 9. 1H NMR (400 MHz, CDCl3); delta 7.70 (dd, 3H, Ar-H), 7.47 (m, 1H, Ar-H), 5.59 (q, 1H, CH-Br), 3.34 (dd, 2H, CH2-CO), 3.03 (dd, 1H, CH2-CO). Mass: m/z calcd. 211, found m/z 212 (M+1)+. HPLC purity (%): 98.58.
Synthesis of 3-azido-indan-1-one To a stirring solution of 3-Bromo indan-1-one (400 mg, 1.90 mmol) in DMF (5 ml) was added sodium azide (1.98 g, 0.03 mol). The reaction was allowed to stir at room temperature for 15 mins. The product was partitioned between water (10 ml) and ether (10 ml). The ether layers were combined and the crude reaction mixture was passed through a plug of flash silica, eluding with petroleum ether:ethyl acetate (9:1). The product was isolated as an orange oil (283 mg, 86%). Vmax/cm-12101 (N3). 1H NMR (CDCl3, 300 MHz) deltaH 2.54 (1H, dd, J=3.1 Hz & 18.9 Hz, CH of CH2), 2.98 (1H, dd, J=7.4 Hz & 19.0 Hz, CH of CH2), 5.0 (1H, dd, J=3 Hz & 7.4 Hz, CHN3), 7.39-7.64 (4H, m, 4*Ar-H). 13C NMR (CDCl3, 75.47 MHz) deltaC 43.0 (CH2), 57.5 (CH), 123.3, 125.8, 129.6, 135.1 (4*Ar-CH), 136.2, 151.0 (2*Ar-C), 201.3 (C=O).
With sodium hydroxide; borane; In tetrahydrofuran; methanol; water;
EXAMPLE 2 dl-3-Benzylamino-1-indanol (Alternative procedure) Cool a solution of benzylamine (3.22 g.) in dry ether (25 ml.) to below 0 C. With stirring under nitrogen add a cooled (below 0 C.) solution of <strong>[40774-41-2]3-bromo-1-indanone</strong> (3.17 g.) in ether (25 ml.) dropwise over 1.5 hours. Store the reaction under nitrogen at -10 C. for one day. Quickly filter the cold solution and add it cold to a stirring solution of one molar borane in tetrahydrofuran (60 ml.) below 0 C. and under nitrogen. Stir the solution for 18 hours at room temperature. Carefully add a solution of water (3.24 ml.) in tetrahydrofuran (20 ml.) dropwise, followed by 8.0 ml. of 5M isopropanolic --HCl, and continue stirring overnight. Store the reaction at -10 C. overnight, then filter the precipitate through filter-aid. Extract the dry solid mixture with methanol-methylene chloride, filter and evaporate the solvents in vacuo. Triturate the resulting solid with cold ethyl acetate, filter and dry to obtain 2.36 g. of the title product as the hydrochloride salt, m.p. 233-235. lambdamaxKBr 3.0 mu (OH). Obtain a sample of the free base of the title product by dissolving a sample of the HCl salt above (1.50 g.) in methanol and treating with solid sodium hydroxide (218 mg.) until complete neutralization. Filter and evaporate in vacuo to obtain the title product as the free base, 0.59 g., m.p. 125-127.
With triethylamine;Sc(OTf)3; In tetrahydrofuran; dichloromethane; ethyl acetate;
Synthesis of 3-(<strong>[387-44-0]7-fluoro-1H-indol</strong>-3-yl)-indan-1-one (Method 1) Triethylamine (4.5 mL; 32 mmol; 1.2 equiv.) was added to 3-bromo-indan-1-one (5.6 g; 27 mmol) in 100 mL THF at 0 C. and stirred 1 h at r.t. The reaction mixture was filtered to remove triethylammonium bromide and concentrated in vacuo to give inden-1-one. <strong>[387-44-0]7-Fluoroindole</strong> (3.3 g, 22 mmol) and Sc(OTf)3 (550 mg, 5 mol %) were added to inden-1-one in 100 mL CH2Cl2 at 0 C. The reaction mixture was allowed to warm to room temperature over night. 100 mL ethyl acetate was added and the mixture was filtered through a silica gel plug and concentrated in vacuo. After flash chromatography (heptane/ethyl acetate, silica gel) 5.9 g 3-(<strong>[387-44-0]7-fluoro-1H-indol</strong>-3-yl)-indan-1-one (82%) was isolated.
3-Bromo-2,3-dihydro-lH-inden-l-one (100 mg, 475 mumol) and cyclohexylamine (94 mg, 951 mumol) were dissolved in 2 inL of dry benzene and stirred under N2 until precipitation ceased (-15 min). The cyclohexylamineEtaBr was removed by filtration. The filtrate was applied to a flash SiO2 column that was developed with 8:1 hexanes-EtOAc to give the title compound as a clear oil (91 mg, 84% yield).
With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; for 1h;
General Procedure: To a solution of (R) or (S)-2-aminotetralin (0.02 g, 0.14 mmol) in DMF (6 mL) was added 2 (0.06 g, 0.28 mmol) and caesium carbonate (0.09 g, 0.28 mmol). The reaction was stirred at room temperature for 1 h, after which time the reaction mixture was partitioned between diethyl ether (3 x 10 mL) and water. The solvent was removed from the organic layer in vacuo. The products, 2a-d, were isolated by means of preparative thin layer chromatography on silica gel (eluant: petroleum ether:ethyl acetate, 7:3).
With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; for 1.0h;
General Procedure: To a solution of (R) or <strong>[2217-42-7](S)-2-aminotetralin</strong> (0.02 g, 0.14 mmol) in DMF (6 mL) was added 2 (0.06 g, 0.28 mmol) and caesium carbonate (0.09 g, 0.28 mmol). The reaction was stirred at room temperature for 1 h, after which time the reaction mixture was partitioned between diethyl ether (3 x 10 mL) and water. The solvent was removed from the organic layer in vacuo. The products, 2a-d, were isolated by means of preparative thin layer chromatography on silica gel (eluant: petroleum ether:ethyl acetate, 7:3).
With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 0 - 50℃; for 3.25h;
a. (±)-3-tert-Butylsulfanyl-indan-l-one (Intermediate 3a) To a solution of 3-bromo-indan-l-one (6.6 g, 31 mmol) in THF (25 mL), tert-butanethiol (7.0 mL, 62 mmol) followed by DIPEA (dropwise addition; 10.6 mL, 62 mmol) were added at 0C. The mixture was stirred at 0C for 45 min, then allowed to warm to RT for 1 h, and then heated at 50C for 90 min. The mixture was concentrated and azeotroped with toluene, partitioned between Et2O/water and extracted with Et2O. Combined organic extracts were dried (Na2SO4) and evaporated. Purification by FCC, using 0-16% EtOAc in cyclohexane as eluent, gave the title compound as a pale yellow solid (3.6 g). NMR (400 MHz, CDC13): 1.47 (9H, s), 2.86 (1H, dd, J 3.4 19.0 Hz), 3.28 (1H, dd, J 3.3, 19.0 Hz), 4.46-4.52 (1H, m), 7.38-7.46 (1H, m), 7.61-7.67 (1H, m), 7.69-7.75 (2H, m).
3.6 g
With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 0 - 50℃; for 3.25h;
To a solution of <strong>[40774-41-2]3-bromo-indan-1-one</strong> (6.6 g, 31 mmol) in THF (25 mL), tert-butanethiol (7.0 mL, 62 mmol) followed by DIPEA (dropwise addition; 10.6 mL, 62 mmol) were added at 0 C. The mixture was stirred at 0 C. for 45 min, then allowed to warm to RT for 1 h, and then heated at 50 C. for 90 min. The mixture was concentrated and azeotroped with toluene, partitioned between Et2O/water and extracted with Et2O. Combined organic extracts were dried (Na2SO4) and evaporated. Purification by FCC, using 0-16% EtOAc in cyclohexane as eluent, gave the title compound as a pale yellow solid (3.6 g). 1H NMR (400 MHz, CDCl3): 1.47 (9H, s), 2.86 (1H, dd, J 3.4 19.0 Hz), 3.28 (1H, dd, J 3.3, 19.0 Hz), 4.46-4.52 (1H, m), 7.38-7.46 (1H, m), 7.61-7.67 (1H, m), 7.69-7.75 (2H, m).
With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In tetrachloromethane; for 2.5h;Reflux;
General procedure: NBS (195 mg, 1.1 mmol) and AIBN (2 mg, 0.01 mmol) were added to a CCl4 solution (4 ml) of the 6-methoxyindanone (162 mg, 1 mmol).The resulting mixture was stirred at reflux temperature for 2.5 h, then cooledand filtered through Celite, which was then washed with CCl4. The filtrate was cooled to 0 C and treated with triethylamine (0.28 mL, 2.0 mmol)overnight, then concentrated in vacuuo. Chromatography of the residue (19~14 EtOAc/hexanes) afforded 97 mg (60%) of enone 1a as the pink oil which solidified as light red solid in refrigerator.
3-(prop-2-yn-1-ylamino)-2,3-dihydro-1H-inden-1-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With potassium carbonate; In acetonitrile; at 60℃; for 3h;Inert atmosphere;
A solution of compound 9 (5 g, 0.0235 mol, 1.0 eq) <strong>[15430-52-1]propargylamine hydrochloride</strong> (2.16 g, 0.0235 mol, 1.0 eq) and K2CO3 (6.50 g, 0.0472 mol, 2.0 eq) were taken in acetonitile (50 mL), then the reaction mixture was heated at 60 C for 3 h. The reaction was monitored by using TLC, after completion of the reaction, acetonitile was evaporated by high vacuum below 50 C added EtOAc and water. Organic layer was separated dried and concentrated. The resultant crude was purified by column chromatography by using EtOAc and n-hexane as a mobile phase resulted 3.1 g compound 7 as a brown thick mass. 1H NMR (400 MHz, DMSO); delta 7.99 (d, 1H, Ar-H), 7.80 (dd, 1H, Ar-H), 7.78-7.68 (dd, 2H, Ar-H), 5.10 (d, 1H, NH-CH), 4.12 (d, 2H, NH-CH2), 3.77 (s, 1H, CH), 3.09 (m, 1H, CO-CH), 2.86 (dd, 1H, COCH). Mass: m/z calcd 185.07, found m/z 186.1 (M+1)+. HPLC purity (%): 98.58.
General procedure: All the alpha-bromo ketones tested for the photolysis experiment were prepared by bromination of the corresponding ketones using CuBr2. The synthetic procedure has been described in our previous paper [7]. Photolysis in solution phase was done with 0.01M solution of the ketones after purging Ar gas through the solution for a few minutes using a typical photolysis setup whose light source was the Pyrex filtered light of a 450W Hanovia medium pressure mercury arc lamp. Photolysis in no solvent condition was done in much simpler way. A sample vial containing either liquid or sold sample was hung next to the photolysis setup and irradiated until completion. For solid samples, the reaction times could be shortened significantly by irradiating the sample doped on a thin glass plate which was simply prepared by dropping acetone solution of a given compound onto any thin glass plate and evaporating the solvent. Structural identification of photoproducts was done either by comparing them with authentic samples when they were available, or by typical spectroscopic identification procedures.
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