* 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] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 2, p. 125 - 128
3
[ 79-22-1 ]
[ 125872-95-9 ]
[ 1204-32-6 ]
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 2, p. 125 - 128
4
[ 68-12-2 ]
[ 125872-95-9 ]
[ 21005-45-8 ]
Reference：
[1] Journal of Organometallic Chemistry, 2011, vol. 696, # 5, p. 1072 - 1083
5
[ 52415-29-9 ]
[ 74-88-4 ]
[ 125872-95-9 ]
Yield
Reaction Conditions
Operation in experiment
91%
Stage #1: With sodium hydride In tetrahydrofuran; mineral oil for 0.333333 h; Inert atmosphere Stage #2: for 0.333333 h; Inert atmosphere
A 1 -round-bottom flask was charged with 6-bromo-lH-indole (14.88 g, 76 mmol) and THF (150 ml) to give a dark maroon solution. The flask was put under a 2 sweep, and sodium hydride (60 wtpercent) (3.64 g, 91 mmol) was added in several portions over 15 min. The resulting mixture was stirred for 20 min, then iodomethane (5.94 ml, 95 mmol) was added via syringe. Within a few minutes, an exotherm was observed. After stirring for 20 min, the mixture was concentrated in vacuo, and the residue was taken up in saturated aq. sodium bicarbonate solution and extracted with DCM (3x). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The crude product was purified by chromatography on silica gel (0 to 40percent EtO Ac/Heptane) to afford 6-bromo-l -methyl- lH-indole (14.44 g, 68.7 mmol, 91 percent yield) as a lightly colored oil. .H NMR (400MHz, CDC13) δ = 7.51 - 7.46 (m, 2 H), 7.24 - 7.19 (m, 1 H), 7.03 (d, J = 3.1 Hz, 1 H), 6.47 (dd, J = 0.9, 3.1 Hz, 1 H), 3.77 (s, 3 H).
84%
Stage #1: With sodium hydride In N,N-dimethyl-formamide; mineral oil for 0.333333 h; Cooling with ice; Inert atmosphere Stage #2: for 0.5 h; Cooling with ice
To a solution of 6-bromo-1H-indole (3.00 g, 15.3 mmol) in DMF (30 mL),NaH (60percent, 734 mg, 18.4 mmol) was added in an ice-water bath, and the mixture was stirred at this temperature for 20 minutes. Then a solution of MeI (1.14 mL, 18.4 mmol) in DMF (10 mL) was added dropwise, and the mixture was stirred at this temperature for 30 minutes. 100 mL of water was added, and the reaction solution was extracted with EtOAc. The EtOAc phase was washed several times with saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography (eluent: pure PE) to obtain the title compound 6-bromo-1-methyl-1H-indole (2.70 g, 84 percent).
79.1%
Stage #1: With sodium hydride In N,N-dimethyl-formamide at 0 - 7℃; for 3 h; Stage #2: at 0 - 25℃; for 2 h;
To a suspension of 60percent NaH (3.61 g, 90.3 mmol) in dry DMF (150 mE) was added 6-bromoindole (11.8 g, 60.191 mmol) at 0° C. in portions. Caution: gas evolved. The inner temperature rose to 7° C. The mixture was re-cooled to 0° C. To the resulting red suspension was stirred at 0° C. for 3 h. CH3I (3.26 g, 23 mmol) was added dropwise at 0° C.-5° C. The reaction suspension was stirred at room temperature (25° C.) for 2 h. TEC (petroleum ether/EtOAc=8/i) showed most of the starting material was consumed and a good spot was formed. The mixture was poured into ice water (200 mE) and extracted with petroleum ether (100 mEx3). The extract was washed with brine (100 mE), dried over Na2 SO4 and concentrated in vacuo to dryness to afford crude (15 g). The crude was purified by silica gel chromatography eluted with EtOAc in petroleum ether from 0 to 10percent to afford J-2 (10 g, 79.1percent) as a slight yellow oil. ‘H NMR (400 MHz, CDC13) ö ppm 7.49-7.47 (m, 2H), 7.22 (d, 1H), 7.03 (d, 1H), 6.46 (d, 1H),3.76 (s, 3H).
63%
With potassium carbonate In acetone at 55℃; for 16 h;
A mixture of 6-bromo-1H-indole (5 g, 25.50 mmol, 1.00 equiv), K2CO3 (7 g, 50.65 mmol, 2.00 equiv), and CH3I (7.3 g, 51.43 mmol, 2.00 equiv) in acetone (100 mL) was stirred for 16 h at 55° C., then cooled to rt, diluted with 100 mL H2O, and extracted with 2×200 mL of EtOAc. The combined organic layers were washed with 100 mL of brine, dried over Na2SO4, concentrated under vacuum, and purified with silica gel chromatography using EtOAc/petroleum ether (1:10) to afford 3.4 g (63percent) of the title compound as a yellow oil. LC-MS: (ES, m/z): 208. 1H NMR (300 MHz, DMSO-d6) δ 7.69 (dt, J=1.6, 0.7 Hz, 1H), 7.49 (dd, J=8.4, 0.6 Hz, 1H), 7.34 (d, J=3.1 Hz, 1H), 7.13 (dd, J=8.4, 1.8 Hz, 1H), 6.43 (dd, J=3.1, 0.9 Hz, 1H), 3.77 (s, 3H).
62%
Stage #1: With potassium carbonate In dimethyl sulfoxide at 20℃; for 0.5 h; Stage #2: at 20℃;
a) 6-bromo-l -methyl- lH-indoleA solution of 6-bromo-l H-indole (1.530 mmol) in dimethyl sulfoxide (10 mL) was treated with potassium carbonate (4.59 mmol) and was stirred at room temperature for 30 min. The solution was then treated with methyl iodide (1.683 mmol) and was stirred at room temperature overnight. The solution was diluted with water (100 mL) and was extracted with ethyl acetate. The combined organic phases were washed with water and brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The crude residue was purified by silica gel chromatography (hexanes) to provide the titlecompound as a yellow oil (62percent). 1H NMR (400 MHz, DMSO-d6) δ ppm 7.70 (s, 1 H) 7.50 (d, J=8.34 Hz, 1 H) 7.35 (d, J=3.03 Hz, 1 H) 7.14 (dd, J=8.34, 1.77 Hz, 1 H) 6.44 (d, J=3.03 Hz, 1 H) 3.78 (s, 3 H).
Reference：
[1] European Journal of Organic Chemistry, 2011, # 20-21, p. 3781 - 3793
[2] Helvetica Chimica Acta, 2006, vol. 89, # 5, p. 936 - 946
[3] Patent: WO2013/25883, 2013, A1, . Location in patent: Page/Page column 41-42
[4] Journal of the American Chemical Society, 2013, vol. 135, # 30, p. 10978 - 10981
[5] ACS Medicinal Chemistry Letters, 2016, vol. 7, # 12, p. 1062 - 1067
[6] Organic Process Research and Development, 2018, vol. 22, # 11, p. 1489 - 1499
[7] Patent: EP3205650, 2017, A1, . Location in patent: Paragraph 0106; 0249; 0250
[8] Patent: US2016/244475, 2016, A1, . Location in patent: Paragraph 0278; 0279
[9] Patent: US2018/162822, 2018, A1, . Location in patent: Paragraph 0500
[10] Patent: WO2011/103546, 2011, A1, . Location in patent: Page/Page column 141-142
[11] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 2, p. 125 - 128
[12] Patent: US2003/125371, 2003, A1,
[13] Patent: US6017945, 2000, A,
[14] Journal of Organometallic Chemistry, 2011, vol. 696, # 5, p. 1072 - 1083
[15] Patent: WO2011/112995, 2011, A1, . Location in patent: Page/Page column 72
[16] Organic Letters, 2012, vol. 14, # 16, p. 4130 - 4133
[17] Chemical Communications, 2012, vol. 48, # 89, p. 11023 - 11025
[18] Patent: US2014/148430, 2014, A1, . Location in patent: Paragraph 0379
[19] Organic Letters, 2016, vol. 18, # 21, p. 5496 - 5499
[20] Chemical Communications, 2017, vol. 53, # 33, p. 4593 - 4596
[21] Organic Letters, 2018, vol. 20, # 16, p. 4898 - 4901
[22] Chemistry - An Asian Journal, 2018, vol. 13, # 18, p. 2664 - 2670
[23] European Journal of Medicinal Chemistry, 2018, vol. 160, p. 120 - 132
6
[ 74-88-4 ]
[ 125872-95-9 ]
Yield
Reaction Conditions
Operation in experiment
100%
Stage #1: With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.333333 h; Stage #2: at 20℃; for 1 h;
Example 29 Synthesis of 6-Bromo-1-methyl-1H-indole (CXLII) To a solution of 6-bromo-1-H-indole (2.5 g, 12.8 mmol) in DMF (10 ml) was slowly added NaH (354 mg, 14.0 mmol) at room temperature. The resulting mixture was stirred for 20 min at RT after which Mel (956 μl, 15.4 mmol) was added. The mixture was stirred for 1 hour at room temperature and then partitioned between DCM and brine. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated to provide 6-Bromo-1-methyl-1H-indole CXLII in quantitative yield (2.7 g).
(methyl-(2-[4-(1-methyl-1H-indol-6-yl)-2-thiophen-2-yl-phenoxy]ethyl)-amino)-acetic acid tert-butyl ester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In tetrahydrofuran; dichloromethane; water; at 95℃; for 4h;
Add (methyl- f 2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-2-thiophen-2- yl-phenoxy]ethyl}-amino)-acetic acid tert-butyl ester prepared as described in Preparation 81 (0.400g, 0.845 mmol) and 2 N aqueous potassium carbonate (2.1 mL, 4.22 mmol) to a solution of <strong>[125872-95-9]6-bromo-1-methyl-1H-indole</strong> (0.195g, 0.92 mmol), [1,1'bis(diphenylphosphino)ferrocene]dichloropalladiurn (II) complex with dichloromethane (1:1) (0.064 g, 0.253 mmol) in tetrahydrofuran (0.5 mL). Heat at 95 C for 4 h. Cool to room temperature and filter through a plug of CeliteNo.. Dilute with ethyl acetate (100 mL), water (50 mL), saturated aqueous sodium chloride (50 mL), dry (sodium sulfate), filter, concentrate and purify (HPLC, eluting with 7: 3 hexanes:ethyl acetate) to give the title compound as a pale yellow oil (150.0 mg). HRMS m/z Calculated: 477.2212; Found: 477.2191
Example 29 Synthesis of 6-Bromo-1-methyl-1H-indole (CXLII) To a solution of 6-bromo-1-H-indole (2.5 g, 12.8 mmol) in DMF (10 ml) was slowly added NaH (354 mg, 14.0 mmol) at room temperature. The resulting mixture was stirred for 20 min at RT after which Mel (956 mul, 15.4 mmol) was added. The mixture was stirred for 1 hour at room temperature and then partitioned between DCM and brine. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated to provide 6-Bromo-1-methyl-1H-indole CXLII in quantitative yield (2.7 g).
With sodium carbonate; In ethanol; hexane; dichloromethane; water; ethyl acetate; toluene;
Step 2 6-(4-Trifluoromethylphenyl)-1-methyl-1H-indole The mixture of <strong>[125872-95-9]6-bromo-1-methyl-1H-indole</strong> (0.216 g, 1.03 mmol), 4-trifluoromethylbenzeneboronic acid (0.216 g, 1.14 mmol), tetrakis(triphenylphosphine) palladium (0.0541 g, 0.0468 mmol) and sodium carbonate (0.438 g, 4.13 mmol) in water (2.5 mL), ethanol (1 mL) and toluene (5 mL) was refluxed for 1.6 hours. The mixture was cooled to room temperature then evaporated to dryness. The residue was partitioned in methylene chloride and water. The organic phase was washed with water, brine, dried over anhydrous magnesium sulfate and evaporated to dryness. The residue was purified by flash chromatography using 0-0.2% ethyl acetate in hexane as an eluant to give the title compound (0.144 g, 51%) as a white solid, mp: -100 C.; 1H-NMR (200 MHz, DMSO-d6): delta8.0 (d, 2H, J=6.6 Hz), 7.8 (d, 3H, J=8.7 Hz), 7.65 (d, 1H, J=8.7 Hz), 7.35-7.5 (m, 2H), 6.45 (d, 1H, J=2.6 Hz), and 3.8-3.95 ppm (m, 3H).
With tert.-butyl lithium;BiCl3; In tetrahydrofuran; diethyl ether; pentane;
EXAMPLE 14 Tri(1-Methylindol-6-yl)bismuthine To a solution of <strong>[125872-95-9]1-methyl-6-bromoindole</strong> (760 mg., 3.6 mmol.) in ethyl ether (15 mL.) at -78 C. was added t-butyllithium (4.4 mL., 7.5 mmol., 1.7M in pentane). After 10 min. a solution of BiCl3 (375 mg., 1.2 mmol.) in THF (4 mL.) was added and the cooling bath removed. The reaction mixture stirred for 4 hr then poured into ice water and extracted with CH2 Cl2. The extracts were combined, backwashed with water, dried with Na2 SO4, filtered, and concentrated in vacuo to a dark oil. The product was crystallized from methanol to afford 290 mg. of the title compound as a tan solid.
With tert.-butyl lithium;BiCl3; In tetrahydrofuran; diethyl ether; pentane;
EXAMPLE 43 Tri(1-methylindol-6-yl)bismuthine To a solution of <strong>[125872-95-9]1-methyl-6-bromoindole</strong> (760 mg., 3.6 mmol.) in ethyl ether (15 mL.) at -78 C. was added t-butyllithium (4.4 mL., 7.5 mmol., 1.7M in pentane). After 10 min. a solution of BiCl3 (375 mg., 1.2 mmol.) in THF (4 mL.) was added and the cooling bath removed. The reaction mixture stirred for 4 hr then poured into ice water and extracted with CH2 Cl2. The extracts were combined, backwashed with water, dried with Na2 SO4, filtered, and concentrated in vacuo to a dark oil. The product was crystallized from methanol to afford 290 mg. of the title compound as a tan solid.
With tert.-butyl lithium;BiCl3; In tetrahydrofuran; diethyl ether; pentane;
EXAMPLE 43 Tri(1-methylindol-6-yl)bismuthine To a solution of <strong>[125872-95-9]1-methyl-6-bromoindole</strong> (760 mg., 3.6 mmol.) in ethyl ether (15 mL.) at -78 C. was added t-butyllithium (4.4 mL., 7.5 mmol., 1.7M in pentane). After 10 min. a solution of BiCl3 (375 mg., 1.2 mmol.) in THF (4 mL.) was added and the cooling bath removed. The reaction mixture stirred for 4 hr then poured into ice water and extracted with CH2 Cl2. The extracts were combined, backwashed with water, dried with Na2 SO4, filtered, and concentrated in vacuo to a dark oil. The product was crystallized from methanol to afford 290 mg. of the title compound as a tan solid.
a) 6-Bromoindole (10.4 g, 53.1 mmol) (prepared according to Moyer, M. P.; Shiurba, J. F.; Rapoport, H. J. Org. Chem. 1986, 51, 5106.) was added in small portions over 30 min to a stirred suspension of sodium hydride (2.96 g, 61.7 mmol, 50% in mineral oil) in dry THF (120 mL) at 0 C. Stirring was continued for another 30 min. lodomethane (4.5 ml, 71.6 mmol) was added dropwise. After 1 h, the mixture was poured into ice-water and extracted with ether (3*200 mL). The combined organic extracts were washed with brine and dried (MgSO4). Evaporation of the solvents and chromatography of the residue over silica gel using hexane gave 6-bromo-1-methyl-1H-indole (10.8 g, 97%).
1-methyl-6-(3-methyl-3H-imidazol-4-yl)-1H-indole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
84%
With triethylamine;tetrakis(triphenylphosphine)palladium (0); In methanol; ethyl acetate; toluene;
b) A solution of <strong>[125872-95-9]6-bromo-1-methyl-1H-indole</strong> (6.2 g, 29.5 mmol) in toluene was degassed by bubbling argon through the solution for 10-20 min. Et3N (8.2 mL, 59 mmol), tetrakis(triphenylphosphine)palladium (0) (681 mg, 0.59 mmol) and 1-methyl-5-(tributylstannyl)imidazole (Gaare, K.; Repstad, T.; Benneche, T.; Undheim, K. Acta Chem. Scan. 1993, 47, 57.) (11.6 g, 31.2 mmol) in toluene (30 mL) were added and the mixture was heated to 120 C. for 18 h until Pd black appeared. The mixture was cooled, filtered through a pad of silica gel and the pad was washed well with EtOAc. The filtrate was evaporated and chromatography of the residue over silica gel using 0.5-1% methanol in EtOAc gave 1-methyl-6-(3-methyl-3H-imidazol-4-yl)-1H-indole (5.21 g, 84%) as an off white crystalline solid.
With n-butyllithium; In tetrahydrofuran; methanol; hexane; water;
a) A solution of n-butyllithium in hexane (1.6 M, 1.7 mL, 27.2 mmol) was added to 6-bromo-1-methyl indole (5.0 g, 23.8 mmol) in dry THF (100 mL) at -78 C. over 30 min. After 30 min, trimethylborate (2.93 g, 28.2 mmol) in dry THF (25 mL) was added. Stirring was continued at -78 C. for 30 min. Methanol (12.5 mL) and water (12.5 mL) were added, and the mixture was stirred at room temperature for 3 h. It was diluted with ether (100 mL), and washed with sulfuric acid (1 N, 2*100 mL) and water (2*100 mL). The aqueous layer was back extracted with ether (2 *100 mL). The combined organic extracts were dried (MgSO4), filtered over a pad of silica gel and the pad was washed with ether (100 mL). The filtrate was concentrated and the crude product was chromatographed over silica gel with 10% to 25% ethyl acetate/hexanes to give 1-methyl-1H-indol-6-yl-boronic acid (2.6 g, 62.5%).
EXAMPLE 103 N6-Methoxy-N6,1-dimethyl-3-{1-(1,3-benzodioxol-5-yl)-2-[(4-methylphenyl)-sulfonamido]-2-oxoethyl}-1H-6-indolecarboxamide STR132 6-Bromo-1-methylindole was treated according to the method of Example 65(a), but using (4-methylphenyl)sulphonamide in place of the sulphonamide of Preparation 11, to give the methyl ester, which was then treated by the method of Example 4 to give the corresponding acid, which was then converted to the title compound by the method of Example 5 using (CH3 O)CH3 NH.
(a) 6-cyano-1-methylindole STR78 Cuprous cyanide (12.8 g, 143 mmol) was added to a stirred solution of <strong>[125872-95-9]6-bromo-1-methylindole</strong> (10 g, 47 mmol) in N-methylpyrrolidinone (60 ml) under a nitrogen atmosphere. The reaction mixture was heated at 150 C. for 48 h. The reaction mixture was cooled and partitioned between ethyl acetate (200 ml) and aqueous ammonia (200 ml of 0.88 M). The organic layer was washed with brine (3*200 ml), dried (MgSO4) and concentrated. Flash column chromatography (elution with 70% hexane/30% ethyl acetate) gave the product as a crystalline white solid (5.3 g). 1 H NMR (400 MHz, CDCl3): delta=3.80 (s, 3 H), 6.60 (s, 1 H), 7.25 (d, 1 H), 7.35 (d, 1 H), 7.70 (d, 2 H). LRMS (Thermospray): 174.1 (MNH4+).
(a) 6-Hydroxymethyl-1-methylindole STR89 To a solution of 6-methoxycarbonyl-1-methylindole (prepared by the method of Example 1(b), but using <strong>[125872-95-9]6-bromo-1-methylindole</strong> in place of 6-bromo-1-ethylindole, 5 g) in tetrahydrofuran (30 ml) at -70 C. under a nitrogen atmosphere, was added diisobutyl aluminium hydride (66 ml of a 1.0 M solution in tetrahydrofuran) dropwise with stirring. The solution was stirred at -70 C. for 15 mins then warmed to room temperature for 2 hours. The mixture was diluted with water (100 ml) and partitioned between ethyl acetate and aqueous sodium hydroxide. The aqueous layer was re-extracted with ethyl acetate and combined organic extracts were dried (MgSO4) and evaporated to give crude product which was purified by flash column chromatography using 80% ethyl acetate/20% hexane eluant to give the subtitle compound as a clear oil which solidified on standing (4.1 g). 1 H NMR (400 MHz, CDCl3): delta=1.60 (s, 1 H), 3.80 (s, 3 H), 4.80 (d, 2 H), 6.45 (s, 1 H), 7.00 (s, 1 H), 7.05 (d, 1 H), 7.35 (s, 1 H), 7.60 (d, 1 H). LRMS (Thermospray): 162.3 (MH+)
4-(thiazol-2-yl)-1-(3-(1-methylindol-6-yl)-propiolyl)piperazine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
Example AAA00108 Synthesis of 4-(thiazol-2-yl)-1-(3-(1-methylindol-6-yl)-propiolyl)piperazine 4-(Thiazol-2-yl)-1-(3-(1-methylindol-6-yl)propiolyl)piperazine was obtained by the reaction of 4-(thiazol-2-yl)-1-propiolylpiperazine [Precursor BBB2] with <strong>[125872-95-9]6-bromo-1-methylindole</strong> under the conditions described in the case of Example AAA35.
Add 5-bromoindole (0.500 g, 2.55 mmol) dropwise to a stirred slurry of sodium hydride (0.098 g, 4.08 mmol) in tetrahydrofuran. (12.75 mL) and stir for 1 h at room temperature. Add iodomethane (0.18 mL, 2.805 mmol) and let stir overnight. Pour over ice and dissolve further with water (100 mL) and extract into ethyl acetate (100 mL), wash with water (3 x 250 mL), saturated aqueous sodium chloride (2 x 250 mL), dry (sodium sulfate), filter, concentrate and purify (HPLC, eluting with 7: 3 hexanes:ethyl acetate) to give the title compound as a white solid (210 mg). HRMS m/z Calculated: 209.9901; Found: 209-9901
With caesium carbonate;copper(l) iodide; 2-acetylcyclohexanone; In N,N-dimethyl-formamide; at 120℃; for 4h;Inert atmosphere;
To 2-(5-trifluoromethyl-pyridin-2-yl)-ethylamine (200 mg, 1.05 mmol) was added <strong>[125872-95-9]6-bromo-1-methyl-1H-indole</strong> (685 mg, 2.10 mmol), cuprous iodide (10 mg, 0.05 mmol) and cesium carbonate (685 mg, 2.1 mmol) under an argon atmosphere. Then DMF (400 mul) and 2-acetylcyclohexanone (28 mul, 0.21 mmol) were added and the reaction mixture was stirred for 4 h at 120 C. After cooling to ambient temperature the reaction mixture was separated between tert-butylmethylether (2×20 ml) and water (15 ml). The combined organic layers were washed with brine (15 ml) and dried over sodium sulfate. Concentration and purification by chromatography (SiO2, heptane:ethyl acetate=100:0 to 67:33) afforded the title compound (114 mg, 34%) as a light brown oil. MS m/e: 320.1 [M+H]+.
methyl 2-(6-bromo-1-methyl-1H-indol-3-yl)-2-oxoacetate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
To a solution of 6-bromo-l -methyl- 1 H-indole (18.0 g, 85.6 mmol) in diethyl ether (180 mL) at 0 C, was added oxalyl chloride (13.1 g, 103 mmol) dropwise under a nitrogen atmosphere. The resulting mixture was allowed to warm to room temperature and stirred for 1 h. After this time, methanol (15 mL) was added and the reaction stirred at roomtemperature further for 24 h. After this time, the reaction was filtered and the filter cake washed with water (20 mL), then cold diethyl ether (20 mL). The filter cake was dissolved in methylene chloride (100 mL) and dried over sodium sulfate. The drying agent was removed by filtration and the filtrate concentrated under reduced pressure to afford methyl 2-(6- bromo-1 -methyl- lH-indol-3-yl)-2-oxoacetate which was used in the next step without purification.
Preparation of 2-(6-bromo-1-methyl-1H-indol-3-yl)ethanol To a solution of 6-bromo-1-methyl-1/1-indole (18.0 g, 85.6 mmol) in diethyl ether (180 mL) at 0 C., was added oxalyl chloride (13.1 g, 103 mmol) dropwise under a nitrogen atmosphere. The resulting mixture was allowed to warn to room temperature and stirred for 1 h. After this time, methanol (15 mL) was added and the reaction stirred at room temperature further for 24 h. After this time, the reaction was filtered and the filter cake washed with water (20 mL), then cold diethyl ether (20 mL). The filter cake was dissolved in methylene chloride (100 mL) and dried over sodium sulfate. The drying agent was removed by filtration and the filtrate concentrated under reduced pressure to afford methyl 2-(6-bromo-1-methyl-1H-indol-3-yl)-2-oxoacetate which was used in the next step without purification. A suspension of methyl 2-(6-bromo-1-methyl-1H-indol-3-yl)-2-oxoacetate (18.0 g, 60.8 mmol) in tetrahydrofuran (200 mL) was treated with 2 M borane dimethylsulfide complex in tetrahydrofuran (121 mL) and stirred at reflux for 5 h. After this time, the reaction was cooled to room temperature, diluted with water (50 mL) and saturated aqueous sodium bicarbonate (100 mL) and extracted with diethyl ether (3*250 mL). The combined organic layers were washed sequentially with water and brine, dried over sodium sulfate, filtered and the filtrate concentrated under reduced pressure to afford 2-(6-bromo-1-methyl-1H-indol-3-yl)ethanol as a white solid: 1H NMR (400 MHz, CDCl3) d 7.46 (d, J=8.4 Hz, 1H), 7.46 (d, J=1.6 Hz, 2H), 7.22 (dd, J=8.4, 1.6 Hz, 1H), 6.92 (s, 1H), 3.88 (t, J=6.4 Hz, 2H), 3.73 (s, 3H), 2.99 (t, J=6.4 Hz, 3H).
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
