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[ CAS No. 244-63-3 ] {[proInfo.proName]}

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Chemical Structure| 244-63-3
Chemical Structure| 244-63-3
Structure of 244-63-3 * Storage: {[proInfo.prStorage]}
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Product Details of [ 244-63-3 ]

CAS No. :244-63-3 MDL No. :MFCD00004956
Formula : C11H8N2 Boiling Point : -
Linear Structure Formula :- InChI Key :AIFRHYZBTHREPW-UHFFFAOYSA-N
M.W : 168.19 Pubchem ID :64961
Synonyms :
Norharman;β-Carboline;NSC 84417;2,9-Diazafluorene;2-Azacarbazole

Calculated chemistry of [ 244-63-3 ]

Physicochemical Properties

Num. heavy atoms : 13
Num. arom. heavy atoms : 13
Fraction Csp3 : 0.0
Num. rotatable bonds : 0
Num. H-bond acceptors : 1.0
Num. H-bond donors : 1.0
Molar Refractivity : 53.6
TPSA : 28.68 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : Yes
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : Yes
Log Kp (skin permeation) : -5.08 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.43
Log Po/w (XLOGP3) : 3.17
Log Po/w (WLOGP) : 2.72
Log Po/w (MLOGP) : 1.62
Log Po/w (SILICOS-IT) : 3.09
Consensus Log Po/w : 2.41

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -3.62
Solubility : 0.0404 mg/ml ; 0.00024 mol/l
Class : Soluble
Log S (Ali) : -3.44
Solubility : 0.0606 mg/ml ; 0.000361 mol/l
Class : Soluble
Log S (SILICOS-IT) : -4.58
Solubility : 0.00443 mg/ml ; 0.0000264 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.46

Safety of [ 244-63-3 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 244-63-3 ]

* 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.

  • Downstream synthetic route of [ 244-63-3 ]

[ 244-63-3 ] Synthesis Path-Downstream   1~84

  • 1
  • [ 16502-01-5 ]
  • [ 244-63-3 ]
YieldReaction ConditionsOperation in experiment
95% With palladium 10% on activated carbon In para-xylene at 145℃; for 72h;
88% With dihydrogen peroxide; iodine In water; dimethyl sulfoxide at 5℃;
83% Stage #1: tetrahydrobetacarboline In tetrahydrofuran at -78℃; for 2h; Stage #2: With oxygen In tetrahydrofuran at 20℃;
82% With palladium 10% on activated carbon for 1.5h; Inert atmosphere; Reflux; 1 A stirred solution of 13 g (0.0756 Mol) 1,2,3,4-tetrahydro-β-carboline, manufactured by tryptamine hydrochloride and glyoxylic acid as described by Ho and Walker (1988), and 2.6 g Pd/C (10%) in 600 ml of cumene were refluxed in a nitrogen atmosphere for 90 min. After addition of 100 ml of ethanol, the hot solution was filtrated, and the coal was extracted thrice by 30 ml of hot ethanol. The combined liquid fractions were concentrated, and the residues was crystallised in toluene to yield 10.5 g (82%) or norharman. Methylation at position 9 was performed as described in the literature (Ho B T, Mcisaac W M, Walker K E, Estevez V, J Pharm Sci 57: 269, 1968) yet with an improved reprocessing. One gram (5.95 mmol) of norharman was dissolved in 10 ml of dried DMF in a nitrogen atmosphere. After that, 0.36 g (14.9 mmol) of sodium hydride were added in form of a 60% dispersion in paraffin at 0° C. After cooling of the reaction mixture down to room temperature, this was cooled down to -10° C., and 0.84 g (5.95 mmol) iodomethane were added. After further stirring for 12 hours, one allowed the mixture to cool down to room temperature once again. All volatile ingredients were removed in reduced pressure. After that, 100 ml of water were added, and the mixture was extracted by 3×50 ml of CHCl3. The combined organic fractions were washed with 5×20 ml of water and were evaporated for drying. The residue was suspended in 100 ml 2 N hydrochloric acid. To separate the educt from the desired methylated product, ion pair exchange extraction of the HCl salt was performed in CHCl3 by a liquid/liquid extractor for two days. After removal of the solvent one yielded 0.7 g (64%) of yellow crystals of 9-methyl-β-carbolinium hydrochloride.[0098]Melting point: 295° C.; GC/MS of the free base: m/z=182 (100%), 167 (5%), 140 (10%), 127 (10%), 113 (5%), 91 (10%). 1H-NMR(HCl salt): δ (ppm) methanol d4, 250 MHz: 4.06 s, 3H, N-CH3; 7.28-7.35, dt, J=1.2; 6.8, 1H, H6; 7.58-7.70, m, 2H, H7, H8; 8.13-8.16, d, J=5.4, 1H, H4; 8.18-8.21, d, J=7.9, 1H H5; 8.31-8.33, d, J=5.4, 1H, H3; 8.89, s, 1H, H1.
81% With palladium 10% on activated carbon In toluene for 5h; Reflux;
78% With carbon dioxide; DBN; Eosin Y In dimethyl sulfoxide at 25 - 30℃; for 48h; Irradiation;
78% With dihydrogen peroxide; iodine In water; dimethyl sulfoxide at 100℃; for 5h;
61% With diphenylselenium bis(trifluoroacetate) In 1,2-dimethoxyethane Ambient temperature;
49.5% With palladium 10% on activated carbon In para-xylene at 145℃; C Preparation of beta-carboline Next, the compound 3 (5.11 g, 29.7 mmol) was added with p-xylene (150.00 mL), reacted with the catalyst of palladium on carbon (Pd/C, 10% , 2.0 mg), and heated to 145° C. and refluxed for 48 hours, followed by cooling to room temperature. The mixture was filtered through celite and washed with methyl alcohol. The solvent was removed by using a rotary vacuum concentrator, and the compound 4 (beta-carboline, 2.48 g) of light yellow solid was obtained. The yield is 49.5%. Spectral data as follow: 1H NMR (400 MHz, d6-DMSO) : δ 11.63 (s, 1H), 8.90 (s, 1H), 8.34 (d, J=4.0 Hz, 1H), 8.24 (d, J=8.0 Hz, 1H), 8.11 (d, J=0.8 Hz, 1H), 7.61-7.54 (m, 2H), 7.24 (m, 1H) ; 13C NMR (100 MHz, d6-DMSO) : δ 140.00, 137.58, 135.46, 133.50, 127.57, 126.91, 121.26, 120.08, 114.11, 111.42.
49.5% With palladium 10% on activated carbon In para-xylene at 145℃; for 48h; 4 Example 4: synthesis of 9H-pyrido[3,4-b]indole Compound 3 (5.11 g, 29.7 mmol) and Pd/C (10%, 2.0 g) were added in 150.00 mL of p-xylene and followed by refluxed at 145° C. for 48 hours, then the temperature was returned to room temperature. The mixture was filtered through celite and then washed with methanol. The solvent was removed in a rotary evaporator to obtain compound 4 (9H-pyrido[3,4-b]indole, i.e. β-carboline, 2.48 g, yield: 49.5%) as a light yellow solid. Spectral data as follow: 1H NMR (400 MHz, d6-DMSO): δ 11.63 (s, 1H), 8.90 (s, 1H), 8.34 (d, J=4.0 Hz, 1H), 8.24 (d, J=8.0 Hz, 1H), 8.11 (d, J=0.8 Hz, 1H), 7.61-7.54 (m, 2H), 7.24 (m, 1H); 13C NMR (100 MHz, d6-DMSO): δ 140.00, 137.58, 135.46, 133.50, 127.57, 126.91, 121.26, 120.08, 114.11, 111.42
With palladium at 165℃;
With selenium at 300℃;
In xylene at 143℃; for 48h;
Multi-step reaction with 2 steps 1.1: triethylamine / dichloromethane 2.1: / tetrahydrofuran / 2 h / -78 °C 2.2: 20 °C
With palladium on activated charcoal In para-xylene

Reference: [1]Peng, Jing; Chen, Chao; Wang, Yong; Lou, Zhenbang; Li, Ming; Xi, Chanjuan; Chen, Hui [Angewandte Chemie - International Edition, 2013, vol. 52, # 29, p. 7574 - 7578][Angew. Chem., 2013, vol. 125, # 29, p. 7722 - 7726,5]
[2]Gaikwad, Sunil; Kamble, Dayanand; Lokhande, Pradeep [Tetrahedron Letters, 2018, vol. 59, # 25, p. 2387 - 2392]
[3]Huang, Yuan-Qiong; Song, Hong-Jian; Liu, Yu-Xiu; Wang, Qing-Min [Chemistry - A European Journal, 2018, vol. 24, # 9, p. 2065 - 2069]
[4]Current Patent Assignee: AUDIOCURE PHARMA GMBH - US2013/28958, 2013, A1 Location in patent: Paragraph 0096; 0097; 0098
[5]Otto, Robert; Penzis, Robert; Gaube, Friedemann; Winckler, Thomas; Appenroth, Dorothea; Fleck, Christian; Tränkle, Christian; Lehmann, Jochen; Enzensperger, Christoph [European Journal of Medicinal Chemistry, 2014, vol. 87, p. 63 - 70]
[6]Riemer, Daniel; Schilling, Waldemar; Goetz, Anne; Zhang, Yu; Gehrke, Sascha; Tkach, Igor; Hollóczki, Oldamur; Das, Shoubhik [ACS Catalysis, 2018, vol. 8, # 12, p. 11679 - 11687]
[7]Shao, Zhihui; Yuan, Shanshan; Li, Yibiao; Liu, Qiang [Chinese Journal of Chemistry, 2022, vol. 40, # 10, p. 1137 - 1143]
[8]Marino, J.P.; Larsen, Robert D. [Journal of the American Chemical Society, 1981, vol. 103, # 15, p. 4642 - 4643]
[9]Current Patent Assignee: YUAN ZE UNIVERSITY - US2017/162794, 2017, A1 Location in patent: Paragraph 0067
[10]Current Patent Assignee: YUAN ZE UNIVERSITY - US2018/40836, 2018, A1 Location in patent: Paragraph 0076
[11]Spaeth; Lederer [Chemische Berichte, 1930, vol. 63, p. 2102,2106]
[12]Marion; Manske [Canadian Journal of Research, Section B: Chemical Sciences, 1938, vol. 16, p. 432,435]
[13]Dantale, Shubhada W.; Söderberg, Björn C. G. [Tetrahedron, 2003, vol. 59, # 29, p. 5507 - 5514]
[14]Li, Yuexian; Prakash, Shimoga R. [Journal of labelled compounds and radiopharmaceuticals, 2005, vol. 48, # 5, p. 323 - 330]
[15]Huang, Yuan-Qiong; Song, Hong-Jian; Liu, Yu-Xiu; Wang, Qing-Min [Chemistry - A European Journal, 2018, vol. 24, # 9, p. 2065 - 2069]
[16]Abdurahman, Alim; Chen, Yingxin; Ai, Xin; Ablikim, Obolda; Gao, Yu; Dong, Shengzhi; Li, Bao; Yang, Bing; Zhang, Ming; Li, Feng [Journal of Materials Chemistry C, 2018, vol. 6, # 42, p. 11248 - 11254]
  • 2
  • [ 244-63-3 ]
  • [ 74-88-4 ]
  • [ 2521-07-5 ]
YieldReaction ConditionsOperation in experiment
77% With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.5h;
65% Stage #1: betacarboline; methyl iodide With sodium hydride In N,N-dimethyl-formamide at 20℃; for 5h; Stage #2: With water In N,N-dimethyl-formamide I; 111; 112; III Example 111; General procedure for the preparation of 9-substituted β-carboline; β-carboline 80 (1.68 g, 10 mmol) was mixed with DMF (50ml) followed by the addition of alkyl halide or aromatics halide (50mmol). The mixture was stirred at room temperature for 5 h. TLC track measurement was conducted. After the reaction was finished, cold water was poured into the reaction mixture, and then extracted with ethyl acetate. The organic phases were combined, washed by water and brine, dried, decolorized with activated carbon, filtered and evaporated. The residues were purified by silica gel column chromatography with petroleum ether/acetone (2: 1) as the eluent.. The collected liquid was concentrated and recrystallized with ethyl acetate. Examples 112 to 115 were all treated according to the above procedures.; Example 112; Synthesis of 9-methyl-β-carboline (81): Afforded white needle solids (1.4g, 77%), and mp 108-109°C.
With sodium hydride
With sodium hydride In tetrahydrofuran
Stage #1: betacarboline With sodium hydroxide In dimethyl sulfoxide at 20℃; Stage #2: methyl iodide In dimethyl sulfoxide for 2h; Reflux;

  • 3
  • [ 244-63-3 ]
  • [ 59444-69-8 ]
YieldReaction ConditionsOperation in experiment
89% With N-Bromosuccinimide; acetic acid at 20℃; for 5h;
86% With N-Bromosuccinimide; acetic acid at 20℃; for 5h; General procedure for the synthesis of eudistomin N (6) General procedure: To the stirred solution of 2a (168.0 mg, 1 mmol,1 equiv) in aceticacid (5 mL) was added NBS (178.0 mg, 1 mmol, 1 equiv) and stirredfor 5 h at room temperature. The mixture was neutralized with1.0 M NaOH solution and extracted with ethyl acetate (2x20 mL)and washed with water (10 mL). The combined extracts were driedover anhydrous Na2SO4, filtered, concentrated under reducedpressure and the crude product was purified by silica gel columnchromatography to afford 6 (212 mg, 86%) as creamish solid; mp266e268 C (lit. mp 265e270 C); IR (KBr): 3210, 3117, 3047, 2934,2837, 2740, 1628, 1562, 1494, 1476,1452, 1432, 1272,1244,1017, 810,798, 601 cm1; 1H NMR (500 MHz, DMSO-d6): d 11.79 (s, 1H), 8.95(s, 1H), 8.52 (d, J 1.5 Hz, 1H), 8.37 (d, J 5.5 Hz, 1H), 8.17 (d,J 5.5 Hz, 1H), 7.67 (dd, J 8.5 Hz, 2.0 Hz, 1H), 7.59 (d, J 8.5 Hz,1H); 13C NMR (125 MHz, DMSO-d6): d 139.2, 138.4, 136.3, 134.4,130.5, 126.5, 124.4, 122.5, 115.0, 114.0, 111.2; EI-MS (70 eV): m/z 245 [M]
83% With N-Bromosuccinimide In acetic acid
80% With N-Bromosuccinimide In N,N-dimethyl-formamide at 20℃; for 12h; 1 Synthesis of Intermediate 2-1 Pyridine [3,4-b] indole (2.0 g, 12 mmol) and N, N-dimethylformamide (30 ml) were added to a three-neck flask followed by slow addition of N-bromosuccinimide (2.3 g, 13 mmol).The reaction was carried out at room temperature for 12 hours, then water was added, filtered and recrystallized from methanol to give 2.3 g of product in 80% yield.
78% With bromine In tetrahydrofuran for 1h; Ambient temperature;
71.47% With N-Bromosuccinimide; acetic acid at 25℃; for 12h; 1.14; 1.38 1.14 Preparation of 6-bromo-9H-pyrido[3,4-b]indole To a mixture of 9H-pyrido[3,4-b]indole (200 mg, 1.19 mmol, 1 eq.) in AcOH (5 mL) was added NBS (211.64 mg, 1.19 mmol, 1 eq.) in one portion at 25 °C. The mixture was stirred at 25 °C for 12 h. LCMS showed that the reaction was complete. The residue was poured into sat. NaHCO3(60 mL) for pH = 8 and the aqueous phase was extracted with EtOAc (3 x 30 mL). The combined organic phase was washed with brine (3 x 30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The mixture was dissolved in EtOAc (10 mL) and PE (60 mL), stirred for 30 mins, and filtered to afford (210 mg, 849.89 μmol, 71.47% yield) as a brown solid.
68% With N-Bromosuccinimide In acetic acid for 2h; Ambient temperature;
27% With bromine; iron In dichloromethane for 1.25h; Ambient temperature;
With N-Bromosuccinimide In tetrahydrofuran for 48h;
With bromine In tetrahydrofuran at 20℃; for 18h;

  • 4
  • [ 244-63-3 ]
  • [ 24223-07-2 ]
YieldReaction ConditionsOperation in experiment
98.6% With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 2h; Compound 21 A solution of b-carboline(10.0 g, 59.5 mmol) in CH2Cl2 (600 mL) was treated with m-chloroperoxybenzoic acid (31.0 g, 179mmol, and stirred at room temperature for 2 hr. 10% potassium dichromate (400mL) was added the reaction mixture, and extracted with chloroform. After thereaction mixture was dried in vacuo, and recrystallized to give 21 (10.8 g, 98.6%). b-carboline,as a staring material, was obtained from Sigma-Aldrich Co., LLC. Through asimilar procedure, compound 22 wasalso synthesized.
95% With 3-chloro-benzenecarboperoxoic acid In ethanol; chloroform Reflux;
89% With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 0 - 20℃;
85% With 3-chloro-benzenecarboperoxoic acid In ethanol; chloroform for 2h; Heating;
67% With 3-chloro-benzenecarboperoxoic acid In chloroform for 2h; Reflux;
With p-bromoperoxybenzoic acid

  • 5
  • [ 6052-68-2 ]
  • [ 244-63-3 ]
YieldReaction ConditionsOperation in experiment
46% With selenium(IV) oxide; acetic acid; for 12h;Reflux; 5 mmol of tryptophan was added to a 100 mL round bottom flask, 50 mL of an aqueous solution containing 1 mL of concentrated hydrochloric acid was added, 30 CStirring to completely dissolved; adding lOmmol formaldehyde to continue reaction 6h,The pH was adjusted to 6 with aqueous sodium bicarbonate solution and filtered to dryness to give 3-carboxy-tetrahydro-beta-carboline. The dried 3-carboxy-tetrahydro-beta-carboline was added to a 100 mL round bottom flask, 50 mL of glacial acetic acid and 7 mmol of selenium dioxide were added, refluxed for 12 h, adjusted to pH 8, extracted with ethyl acetate and concentrated. Acetone was recrystallized to the target beta-carboline (2.3 mmo 1, yield 46%)
With human myeloperoxidase; dihydrogen peroxide; at 37℃; for 0.666667h;pH 7.0;Enzymatic reaction;Kinetics; Fresh solutions of peroxidases were prepared to make: 0.32 muM HRP, 0.178 muM LPO or 0.0126 muM MPO in 50 mM phosphate buffer, pH 7 (0.5 ml final volume for MPO or 1 ml for HRP or LPO) containing in separate, 1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (THCA) or 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (MTCA) in a range from 0 to 2 mM. The reaction was initiated by addition of H2O2 solution (5-500 muM, final concentration), and the samples incubated at 37 C for 40 min. Following addition of HClO4 + methanol (1/1) (50 or 100 mul, 10% v/v), the tubes were centrifuged at 10,000 rpm, 10 min, and the reaction products were analyzed by HPLC and HPLC-MS. Selected concentrations of H2O2 used for kinetic studies with tetrahydro-beta-carbolines were as follows: 100 muM for HRP/THCA, 50 muM for HRP/MTCA; 10 muM for LPO/THCA; 25 muM for LPO/MTCA, and 25 muM for THCA/MPO and MTCA/MPO. Incubations were at least in duplicate and control reactions were carried out in absence of enzyme, H2O2 or tetrahydro-beta-carbolines, and in presence of catalase (0.05-0.2 mg prot./ml). Reactions were also carried out in presence of 1 mM ascorbic acid, 1 mM sodium azide, 1 mM hydroxylamine or excess H2O2 (2 mM) as inhibitors of peroxidase and substrate (250 muM). On the other hand, cytochrome P450 and catalase (heme proteins), and glutathione peroxidase were incubated with tetrahydro-beta-carbolines to assess possible oxidation, as follows: (a) 0.2 ml phosphate buffer 50 mM, pH 7.0, containing a mixture of cytochrome P450s (Supermix) (20 pmol P450) and THCA and/or MTCA (250 muM), with or without NADPH (1 mM) and H2O2 (50-500 muM); (b) 1 ml phosphate buffer 50 mM, pH 7, containing catalase (0.05-0.2 mg prot./ml), THCA or MTCA (250 muM) and H2O2 (100-500 muM); (c) 1 ml phosphate buffer 50 mM (pH 7), containing glutathione peroxidase (9.6 mug prot./ml), H2O2 (50 muM) and MTCA or THCA (500 muM). The mixtures were incubated (37 C, 25 min), the reaction stopped with 10 % v/v HClO4/methanol (1:1), centrifuged and analyzed by RP-HPLC-DAD.
  • 6
  • [ 244-63-3 ]
  • [ 30684-41-4 ]
YieldReaction ConditionsOperation in experiment
95% With ammonia; sodium amide
79% With sodium amide In <i>N</i>,<i>N</i>-dimethyl-aniline at 160℃; for 24h; Inert atmosphere; 1-Amino-β-carboline: Sodium amide (640 mg, 16 mmol) was added portion-wise to a solution of β-carboline (690 mg, 4.1 mmol) in N,N-dimethylaniline (20 ml). The reaction mixture was heated at 160°C for 24 h. The contents of the flask were allowed to cool, and 10 ml of 5% sodium hydroxide solution and 20 ml of water were added cautiously. Hexane (40 ml) was poured into the reaction mixture. The formed precipitate was collected by filtration. The residue was dried in vacuo and purified using NH-silica gel column chromatography (chloroform/methanol = 100:1 to 20:1) to give title compound. This purified product was further recrystallized from toluene and dried in vacuo to provide very pure compound. Yield; 79%, white solid, mp; 202-205°C. 1H NMR (500 MHz, DMSO-d6): d 6.07 (s, 2H), 7.16 (t, 1H, J=8.2 Hz), 7.29 (d, 1H, J=5.5 Hz), 7.44 (t, 1H, J=8.2 Hz), 7.58 (d, 1H, J=8.2 Hz), 7.70 (d, 1H, J=5.5 Hz), 8.04 (d, 1H, J=8.2 Hz), 11.02 (s, 1H); 13C NMR (125 MHz, DMSO-d6): d 104.8, 111.9, 118.9, 121.2, 121.7, 122.8, 126.4, 126.6, 136.5, 139.0, 146.6; MS (FAB): m/z 184 [M+H]+.
  • 8
  • [ 239137-41-8 ]
  • [ 244-63-3 ]
YieldReaction ConditionsOperation in experiment
70% With potassium <i>tert</i>-butylate; ammonia for 1h; Inert atmosphere; Irradiation;
61% With sodium carbonate In N,N-dimethyl-formamide Heating;
28% With potassium phosphate; palladium diacetate at 170℃; for 2h; Inert atmosphere; Microwave irradiation; 2 Step 2: 9H-pyrido[3,4-b]indole A mixture of 4-bromo-N-phenylpyridin-3-amine (500 mg, 2.0 mmol), palladium acetate (89 mg, 0.4 mmol) and K3PO4 (1.27 g, 6.0 mmol) in DMA (10 mL) was degassed with nitrogen, heated to 170° C. and stirred for 2 hours under microwave condition. The reaction was cooled to r.t and filtered. The filtrate was purified via reverse phase column chromatography (CH3CN/H2O=5%-80%) to give 9H-pyrido[3,4-b]indole (120 mg, 28% yield) as white solid. 1H NMR (400 MHz, DMSO-d6) δ 12.57 (s, 1H), 9.27 (s, 1H), 8.74 (d, J=6.1 Hz, 1H), 8.58 (d, J=6.1 Hz, 1H), 8.51 (d, J=8.0 Hz, 1H), 7.82-7.76 (m, 2H), 7.55-7.27 (m, 1H). LC/MS (ESI, m/z): [M+1]+=169.2.
  • 9
  • [ 244-63-3 ]
  • [ 15441-06-2 ]
  • methyl 3-(9-(pyrido[3,4-b]indolyl))propionate [ No CAS ]
  • 11
  • [ 244-63-3 ]
  • [ 46857-11-8 ]
  • [ 378238-38-1 ]
YieldReaction ConditionsOperation in experiment
91% With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane
91% With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 2h;
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 3h;
  • 12
  • [ 244-63-3 ]
  • [ 68-95-1 ]
  • [ 316789-84-1 ]
  • 13
  • [ 244-63-3 ]
  • [ 52574-06-8 ]
  • [ 474433-39-1 ]
  • 14
  • [ 244-63-3 ]
  • [ 100-39-0 ]
  • 2,9-dibenzyl-β-carbolinium bromide [ No CAS ]
YieldReaction ConditionsOperation in experiment
76% With sodium hydride In N,N-dimethyl-formamide at 50 - 60℃; for 2h;
Stage #1: betacarboline In N,N-dimethyl-formamide at 20℃; for 0.166667h; Stage #2: benzyl bromide With sodium hydride In N,N-dimethyl-formamide at 60℃; for 8h; 2.2.2. General procedure for the synthesis of compounds 4a-h General procedure: Compounds 4a-h were synthesized according to the modified reported procedure [37] . A mixture of -carbolines ( 3 , 0.2 g, 5.0 mmol) and anhydrous DMF (12.5 mL) was stirred at room temper- ature for 10 minutes. 60% NaH (7.5 mmol) and substituted ben- zyl bromide (10.0 mmol) were added. The mixture was heated for 3 hrs at 60 °C than continued with refluxed for 5 hrs. Upon completion, the solution was poured into ice-cold water (H2O, 100 mL) and extracted with ethyl acetate (2 ×100 mL). The combined organic layers were washed with water, brine, dried over anhydrous sodium sulphate, filtered and evaporated to af- ford compounds 4a-h as solid powder/crystals. Pure compounds 4a-h were obtained from recrystallization using ethanol. Phys- ical properties, FT-IR, NMR, Mass and Elemental analysis data for compounds 4a-h have been placed in the supplementary file.
  • 17
  • [ 74-96-4 ]
  • [ 244-63-3 ]
  • 2,9-diethyl-β-carbolinium bromide [ No CAS ]
YieldReaction ConditionsOperation in experiment
63% Stage #1: ethyl bromide; betacarboline With sodium hydride In N,N-dimethyl-formamide at 50 - 60℃; for 2h; Stage #2: With water In N,N-dimethyl-formamide I; 119; III Synthesis of 2,9-diethyl-(β-carbolinium bromate (88) Compound 80 (0.84g, 5mmol) was mixed with DMF (30ml) and 60% NaH (0.3g, 15mmol) followed by the addition of ethyl bromide (30 mmol). The mixture was stirred and reacted at 50 to 60 °C for 2 h. The reaction mixture was poured into 100ml cold water and extracted with ethyl acetate. The extract was dried with anhydrous sodium sulfate and then concentrated to afford yellow solids. The solids were recrystallized with anhydrous ethanol to afford yellow solids (1.1g, 63%), mp > 270°C.
  • 18
  • [ 74-83-9 ]
  • [ 244-63-3 ]
  • 2,9-dimethyl-β-carbolinium bromide [ No CAS ]
YieldReaction ConditionsOperation in experiment
73% Stage #1: methyl bromide; betacarboline With sodium hydride In N,N-dimethyl-formamide at 50 - 70℃; for 0.5h; Stage #2: With water In N,N-dimethyl-formamide I; 118; III Synthesis of 2,9-dimethyl-β-carbolinium bromate (87) Compound 80 (0.84g, 5mmol) was mixed with DMF (30ml) and 60% NaH (0.3g, 15mmol) followed by the addition of methyl bromide (30 mmol). The mixture was stirred and reacted at 50 to 70 °C for 0.5 hour. The reaction mixture was poured into 100ml cold water and extracted by ethyl acetate. The extract was dried with anhydrous sodium sulfate and then concentrated to afford yellow solids. The solids were recrystallized with anhydrous ethanol to afford white solids (1.8g, 73%), mp >270 °C .
  • 19
  • [ 84518-77-4 ]
  • [ 244-63-3 ]
YieldReaction ConditionsOperation in experiment
60% Stage #1: ethyl 1,2,3,4-tetrahydro-β-carboline-3-carboxylate With selenium(IV) oxide In acetic acid for 12h; Heating / reflux; Stage #2: With sodium hydroxide In water I; 110; III Synthesis of β-carboline (80) Compound 10b (24.4g, 0.1 mol) was mixed with glacial acetic acid (500 ml) followed by the addition of selenium dioxide (20g, 0.2mol). The mixture was refluxed for 12 h. The glacial acetic acid was removed I . 1M NaOH solution (200ml) was added into the residues, then the mixture was extracted with ethyl acetate. The organic phases were combined, washed by 1M NaOH solution, water and brine, dried, decolorized with activated carbon, filtered, evaporated and recrystallized with ethyl acetate to afford white solids (10.0g, 60%), and mp 197-198°C (reference [20]:198 to 200°C).
With selenium(IV) oxide; acetic acid Reflux;
  • 20
  • [ 244-63-3 ]
  • [ 3449-48-7 ]
  • [ 106-93-4 ]
  • [ 73166-16-2 ]
YieldReaction ConditionsOperation in experiment
90% With sodium hydroxide; In water; toluene; The amount of the tetrabutylammoniumhydrogensulfate used as catalyst can be reduced to 5 m moles per 1 mole of the carbazoline employed. During the procedure the reaction takes twice as long. In lieu of the excess dibromoethane it is possible to use other solvents which are immiscible in water and inactive under the conditions of the reaction, for example toluene, benzene or chlorobenzene. 199 g. (1 mole) of 6-methyl-1,2,3,4-tetrahydro-carbazol-1-one and 376 g. (2 moles) of 1,2-dibromoethane are dissolved in 1000 ml. of toluene and stirred together with 1000 ml. of sodium hydroxide solution and 4.25 g. (12,5 m moles) of tetrabutylammoniumhydrogensulfate for 10 hours at 60 C. After evaporating the aqueous layer, distilling off the solvent and recrystallizing the residual crude product, 275 g. of 6-methyl-9-(2-bromoethyl)-1,2,3,4-tetrahydrocarbazol-1-one (90% of the theoretical) melting at 102 to 103 C. are obtained.
  • 21
  • [ 244-63-3 ]
  • [ 938469-95-5 ]
  • [ 938470-02-1 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate In Tetraethylene glycol dimethyl ether at 180℃; for 8h; 7 [EXAMPLE 7: Target Compound 12]; [Show Image] Under a nitrogen stream, 9H-pyrido[3,4-b]indole (2.8 g), Target Compound 3 (2.47 g), a copper powder (1.06 g), potassium carbonate (4.6 g), and tetraglyme (8 mL) were allowed to react at 180°C for 8 hours with stirring. After the completion of the reaction, chloroform was added to the reaction mixture. The insoluble matter was filtered off. After the filtrate was concentrated, the resulting precipitate was subjected to suspension washing with methanol and purified by silica-gel column chromatography (an ethyl acetate/methylene chloride mixture → an ethanol/methylene chloride mixture) to yield Target Compound 12 (1.27 g). DEI-MS: m/z = 617 (M - H)+ DCI-MS: m/z = 619 (M + H)+ This compound had a glass transition temperature of 135°C, a melting point of 221°C, and a vaporization temperature of 499°C. This compound was dissolved in toluene in an amount of 3 percent by weight or more. The difference in energy between the excited triplet state and the ground state of this compound was 2.96 eV.
  • 22
  • [ 111-24-0 ]
  • [ 244-63-3 ]
  • [ 1225056-70-1 ]
YieldReaction ConditionsOperation in experiment
54% Stage #1: betacarboline With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.333333h; Stage #2: 1,5-dibromo-pentane In N,N-dimethyl-formamide at 20℃; 1 5.5 General procedure for the preparation of bivalent β-carbolines 18-34 General procedure: To a stirred solution of monovalent β-carbolines 1-17 (2.0 mmol) in anhydrous DMF (30 ml) was added 60% NaH (0.4 g, 10 mmol). After stirring for 20 min at room temperature, the appropriate dibromoalkane (1.0 mmol) was added. And then the reaction mixture was stirred at room temperature for 8-20 h. After completion of the reaction as indicated by TLC, the solution was poured into ice-water and extracted with CH2Cl2. The combined organic layer was washed with water and brine, dried over anhydrous Na2SO4, filtered and evaporated in vacuum. The residue was purified by column chromatography with CH2Cl2/MeOH (50:1) to successfully afford the desirable target products.
16% With sodium hydroxide In dimethyl sulfoxide at 20℃; for 4h;
  • 23
  • [ 244-63-3 ]
  • 3,6-dibromo-β-carboline [ No CAS ]
  • [ 144434-79-7 ]
YieldReaction ConditionsOperation in experiment
1: 13% 2: 8% With N-Bromosuccinimide In dichloromethane at 20℃; Darkness;
1: 13% 2: 8% With N-Bromosuccinimide; silica gel In dichloromethane at 20℃; for 2.5h; Darkness; 13.1 Step 1.
Synthesis of 3,6-Dibromo-β-carboline
Following a literature procedure (Ponce, M. A.; Erra-Balsells, R. J. Heterocyclic Chem. 2001, 38, 1087) β-Carboline (0.100 g, 0.595 mmol) and SiO2 (1.00 g) were suspended in CH2Cl2 (15 mL). N-Bromosuccinimde (0.212 g, 1.189 mmol) was dissolved in CH2Cl2 (15 mL) and the solution was added to the carboline mixture slowly via syringe in the absence of light. The reaction was stirred at ambient temperature for 2.5 h, after which the silica gel was filtered off and washed 3*CH2Cl2. The combined organic layer was extracted with 0.1 M NaOH and saturated aqueous NaCl, dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by chromatography (SiO2, 0-100% EtOAc/Hexane) to afford the desired 3,6-dibrominated carboline (25 mg, 13%) as well as 6,8-dibrominated carboline (15 mg, 8%) and the tribrominated carboline (36 mg, 19%). (1437) 1H NMR (d6-DMSO, 500 MHz) δ 8.72 (s, 1H), 8.58 (d, 1H, J=1.5 Hz), 8.48 (s, 1H), 7.70 (dd, 1H, J=1.5, 9.0 Hz), 7.58 (d, 1H, J=9.0 Hz). (1438) ESI m/z 326.9 ([M+H]+, C11H7Br2N2 requires 326.9).
  • 24
  • [ 50-00-0 ]
  • [ 244-63-3 ]
  • [ 20127-63-3 ]
YieldReaction ConditionsOperation in experiment
30% With ferrous(II) sulfate heptahydrate; dihydrogen peroxide In water at 10 - 15℃; for 1h; regioselective reaction;
  • 25
  • [ 244-63-3 ]
  • [ 1309919-38-7 ]
YieldReaction ConditionsOperation in experiment
86% With chlorosulfonic acid at 5 - 20℃; (1) Compound 6 General procedure: Compound 6: In a 25 mL single-necked, round-bottomed flask equipped with a magnetic stirrer, 4.0 mL of chlorosulfonic acid (60.20 mmol) was added. Cool the reaction mixture to 5 °C and compound 5 (0.53 g, 2.51 mmol) was added through several times. After addition, the reaction mixture was stirred at rt for 0.5 h. Then the reaction mixture was slowly poured into 200 mL of cooled water. The yellow solid precipitated and collected on a filter, washed with water (20 mL × 2). The crude product can be used in next step without further purification (0.66 g, yield 85.0%).
With chlorosulfonic acid at 0℃; for 1h; Inert atmosphere;
  • 26
  • [ 42438-90-4 ]
  • [ 244-63-3 ]
YieldReaction ConditionsOperation in experiment
83% With iron(III) chloride In N,N-dimethyl-formamide at 130℃; for 1h; Green chemistry; General procedure for the synthesis of b-carbolines viadecarboxylative/dehydrogenative aromatization General procedure: To a mixture of tetrahydro-b-carboline 1/3 (1 mmol) in DMF(5 mL), FeCl3 (10 mol%, 16.2 mg) was added. The reaction wasstirred at 130 C. After completion of the reaction (TLC control), themixture was cooled to room temperature and water (10 mL) wasadded. The reaction mixture was then extracted with EtOAc(2 20 mL) and the combined EtOAc layer was washed with brine solution (5 mL). The organic layerwas dried over anhydrous Na2SO4and concentrated under reduced pressure. The crude product waspurified over silica gel column chromatography (100e200 meshsize) using a gradient eluent of hexane/EtOAc mixture to affordpure b-carboline 2/4.
81% With copper dichloride In N,N-dimethyl-formamide at 130℃; for 1h; General Procedure General procedure: To 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylicacid (1 mmol) in DMF (10 mL) was added CuCl2 (10 mol%)and stirred for 1 h at 130 °C. On completion of the reaction(TLC), H2O (5 mL) was added to the reaction, and themixture was basified to pH 9 with 1 M NaOH. The aqueouslayer was extracted with CH2Cl2 (3 × 20 mL), and thecombined organic layers were dried over anhydrous Na2SO4.The CH2Cl2 was evaporated, and the residue was purified bychromatography which afforded pure 9H-pyrido[3,4-b]indole(2a) as a white solid. 1H NMR (500 MHz, DMSO-d6): δ =11.63 (1 H, s), 8.89 (d, J = 0.5 Hz, 1 H), 8.31 (d, J = 5.5 Hz,1 H), 8.2 (d, J = 7.0 Hz, 1 H), 8.09 (dd, J1 = 0.5 Hz, J2 = 1.0Hz, 1 H), 7.60 (d, J = 10.0 Hz, 1 H), 7.55-7.53 (m, 1 H),7.24-7.21 (m, 1 H). 13C NMR (125 MHz, DMSO-d6): δ =140.5, 137.9, 135.9, 133.7, 128.5, 127.6, 121.7, 120.4,119.4, 114.7, 112.1. GC-MS: 168 [M+]
80% With N-chloro-succinimide; triethylamine In N,N-dimethyl-formamide at 20℃; for 0.5h;
77% With [bis(acetoxy)iodo]benzene In N,N-dimethyl-formamide at 20℃; for 1h;
75% With selenium(IV) oxide; acetic acid for 12h; Reflux;
72% With [bis(acetoxy)iodo]benzene In N,N-dimethyl-formamide at 20℃; 3.β-Carbolines (12a-c)4 General procedure: To a stirred solution of tetrahydro-β-carboline acids (10 and 11a-b, 10 mmol) in DMF (5 mL) was slowly added iodobenzene diacetate (6 g, 20 mmol) and the resulting mixture was stirred at room temperature for 1 h. After completion of the reaction as indicated by TLC, the contents were neutralized with saturated NaHCO3 solution and extracted with dichloromethane (3 × 50 mL). The combined organic layer was washed with brine solution (50 mL), dried over anhydrous Na2SO4 and the solvent was evaporated under reduced pressure. The obtained crude product was purified by column chromatography using ethyl acetate and hexane (7:3) to afford the b-carbolines 12a-c in 65-72% yields.
55% With dihydrogen peroxide; iodine In water; N,N-dimethyl-formamide at 100℃; for 5h; 4.1.1. General procedure for the synthesis of 1-phenyl-9H-pyrido[3,4-b]indole (2a) General procedure: To a mixture of 1-phenyl-tetrahydro-β-carboline-3-carboxylicacid 1a (1 mmol, 292 mg), and I2 (10 mol%, 25.4 mg) in DMF (5 mL) was added 30% aqueous solution of H2O2 (0.113 mL,1 mmol). The reaction was stirred at 100°C for 1 h. After completion of the reaction (TLC), the reaction mixture was treated with a 5% hyposolution (5 mL). The reaction mixture was then extracted with ethylacetate (2 20 mL) and the combined ethyl acetate layer was washed with water (2x5 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was puried over column chromatography to afford 1-phenyl-β-carboline 2a (210 mg, 86% yield).

  • 27
  • [ 110-52-1 ]
  • [ 244-63-3 ]
  • [ 1415723-44-2 ]
YieldReaction ConditionsOperation in experiment
46% Stage #1: betacarboline With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.333333h; Stage #2: 1,4-dibromo-butane In N,N-dimethyl-formamide at 20℃; 1 5.5 General procedure for the preparation of bivalent β-carbolines 18-34 General procedure: To a stirred solution of monovalent β-carbolines 1-17 (2.0 mmol) in anhydrous DMF (30 ml) was added 60% NaH (0.4 g, 10 mmol). After stirring for 20 min at room temperature, the appropriate dibromoalkane (1.0 mmol) was added. And then the reaction mixture was stirred at room temperature for 8-20 h. After completion of the reaction as indicated by TLC, the solution was poured into ice-water and extracted with CH2Cl2. The combined organic layer was washed with water and brine, dried over anhydrous Na2SO4, filtered and evaporated in vacuum. The residue was purified by column chromatography with CH2Cl2/MeOH (50:1) to successfully afford the desirable target products.
46% With sodium hydride In N,N-dimethyl-formamide at 60℃; 1 Synthesis process of bis β-carboline compound (1-4): General procedure: β- carboline (0.45g, 2mmol), DMF (30ml), 60% NaH (5mmol) anddihaloalkanea (1mmol) was added, 8-20h allowed to stir to react the reaction mixture at 60 ,tracking detection by TLC ( eluent: methanol) was carried out. After completion of the reaction, the reactionmixture was poured into water 100ml, and extracted withdichloromethane, extractswere combined, washed with water, washed with saturated brine, dried overanhydrous sodium sulfate, and concentrated under reduced pressure to drynessand purified by silica gel column dichloromethane by chromatography: methanol =50: 1 was sequentially concentrated under reduced pressure to give a white solid. 1,4-bis (β- carboline-9-yl) butane(1): The yield was 46%., MP> 270 ° C.; IR( KB r) 3041,2940,1622,1556,1467,1445,1328,1247,1025,819,750,730; 1H-NMR (500MHz, DMSO-d6) delta 9.03 ( 2H, s), 8.36 (2H, d, J = 5.0Hz), 8.23 (2H, d, J =8.0Hz), 8.09 (2H, d, J = 5.0Hz), 7.65 (2H, d, J = 8.5Hz), 7.56 (2H, t, J =7.5Hz), 7.25 (2H, t, J = 7.5Hz), 4.49 (4H , t, J = 7.5Hz), 1.87-1.92 (4H, m);13C NMR (100 MHz, CDCl3): δ 141.0, 139.0, 136.4, 131.8, 128 .5, 122.0, 121.1,119.8, 114.7, 109.3, 43.0, 27.0. ESI-MS m / z: 391.3 (M +).
  • 28
  • [ 629-03-8 ]
  • [ 244-63-3 ]
  • [ 1415723-45-3 ]
YieldReaction ConditionsOperation in experiment
52% Stage #1: betacarboline With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.333333h; Stage #2: 1 ,6-dibromohexane In N,N-dimethyl-formamide at 20℃; 1 5.5 General procedure for the preparation of bivalent β-carbolines 18-34 General procedure: To a stirred solution of monovalent β-carbolines 1-17 (2.0 mmol) in anhydrous DMF (30 ml) was added 60% NaH (0.4 g, 10 mmol). After stirring for 20 min at room temperature, the appropriate dibromoalkane (1.0 mmol) was added. And then the reaction mixture was stirred at room temperature for 8-20 h. After completion of the reaction as indicated by TLC, the solution was poured into ice-water and extracted with CH2Cl2. The combined organic layer was washed with water and brine, dried over anhydrous Na2SO4, filtered and evaporated in vacuum. The residue was purified by column chromatography with CH2Cl2/MeOH (50:1) to successfully afford the desirable target products.
  • 29
  • [ 244-63-3 ]
  • [ 4549-31-9 ]
  • [ 1415723-46-4 ]
YieldReaction ConditionsOperation in experiment
51% Stage #1: betacarboline With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.333333h; Stage #2: 1,7-dibromoheptane In N,N-dimethyl-formamide at 20℃; 1 5.5 General procedure for the preparation of bivalent β-carbolines 18-34 General procedure: To a stirred solution of monovalent β-carbolines 1-17 (2.0 mmol) in anhydrous DMF (30 ml) was added 60% NaH (0.4 g, 10 mmol). After stirring for 20 min at room temperature, the appropriate dibromoalkane (1.0 mmol) was added. And then the reaction mixture was stirred at room temperature for 8-20 h. After completion of the reaction as indicated by TLC, the solution was poured into ice-water and extracted with CH2Cl2. The combined organic layer was washed with water and brine, dried over anhydrous Na2SO4, filtered and evaporated in vacuum. The residue was purified by column chromatography with CH2Cl2/MeOH (50:1) to successfully afford the desirable target products.
  • 30
  • [ 244-63-3 ]
  • [ 4549-32-0 ]
  • [ 1415723-47-5 ]
YieldReaction ConditionsOperation in experiment
44% Stage #1: betacarboline With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.333333h; Stage #2: 1,8-dibromooctane In N,N-dimethyl-formamide at 20℃; 1 5.5 General procedure for the preparation of bivalent β-carbolines 18-34 General procedure: To a stirred solution of monovalent β-carbolines 1-17 (2.0 mmol) in anhydrous DMF (30 ml) was added 60% NaH (0.4 g, 10 mmol). After stirring for 20 min at room temperature, the appropriate dibromoalkane (1.0 mmol) was added. And then the reaction mixture was stirred at room temperature for 8-20 h. After completion of the reaction as indicated by TLC, the solution was poured into ice-water and extracted with CH2Cl2. The combined organic layer was washed with water and brine, dried over anhydrous Na2SO4, filtered and evaporated in vacuum. The residue was purified by column chromatography with CH2Cl2/MeOH (50:1) to successfully afford the desirable target products.
  • 31
  • [ 244-63-3 ]
  • [ 74-88-4 ]
  • [ 752213-27-7 ]
YieldReaction ConditionsOperation in experiment
64% Stage #1: betacarboline With sodium hydride In N,N-dimethyl-formamide; paraffin oil at 0 - 20℃; Inert atmosphere; Stage #2: methyl iodide In N,N-dimethyl-formamide; paraffin oil at -10 - 20℃; for 12h; Stage #3: With hydrogenchloride In water 1 Synthesis of 9-methyl-β-carboline A stirred solution of 13 g (0.0756 Mol) 1,2,3,4-tetrahydro-β-carboline, manufactured by tryptamine hydrochloride and glyoxylic acid as described by Ho and Walker (1988), and 2.6 g Pd/C (10%) in 600 ml of cumene were refluxed in a nitrogen atmosphere for 90 min. After addition of 100 ml of ethanol, the hot solution was filtrated, and the coal was extracted thrice by 30 ml of hot ethanol. The combined liquid fractions were concentrated, and the residues was crystallised in toluene to yield 10.5 g (82%) or norharman. Methylation at position 9 was performed as described in the literature (Ho B T, Mcisaac W M, Walker K E, Estevez V, J Pharm Sci 57: 269, 1968) yet with an improved reprocessing. One gram (5.95 mmol) of norharman was dissolved in 10 ml of dried DMF in a nitrogen atmosphere. After that, 0.36 g (14.9 mmol) of sodium hydride were added in form of a 60% dispersion in paraffin at 0° C. After cooling of the reaction mixture down to room temperature, this was cooled down to -10° C., and 0.84 g (5.95 mmol) iodomethane were added. After further stirring for 12 hours, one allowed the mixture to cool down to room temperature once again. All volatile ingredients were removed in reduced pressure. After that, 100 ml of water were added, and the mixture was extracted by 3×50 ml of CHCl3. The combined organic fractions were washed with 5×20 ml of water and were evaporated for drying. The residue was suspended in 100 ml 2 N hydrochloric acid. To separate the educt from the desired methylated product, ion pair exchange extraction of the HCl salt was performed in CHCl3 by a liquid/liquid extractor for two days. After removal of the solvent one yielded 0.7 g (64%) of yellow crystals of 9-methyl-β-carbolinium hydrochloride.[0098]Melting point: 295° C.; GC/MS of the free base: m/z=182 (100%), 167 (5%), 140 (10%), 127 (10%), 113 (5%), 91 (10%). 1H-NMR(HCl salt): δ (ppm) methanol d4, 250 MHz: 4.06 s, 3H, N-CH3; 7.28-7.35, dt, J=1.2; 6.8, 1H, H6; 7.58-7.70, m, 2H, H7, H8; 8.13-8.16, d, J=5.4, 1H, H4; 8.18-8.21, d, J=7.9, 1H H5; 8.31-8.33, d, J=5.4, 1H, H3; 8.89, s, 1H, H1.
  • 32
  • [ 244-63-3 ]
  • [ 22945-96-6 ]
YieldReaction ConditionsOperation in experiment
Stage #1: betacarboline With sodium hydride In N,N-dimethyl-formamide; paraffin oil at 0 - 20℃; Inert atmosphere; Stage #2: prolyl-X, X=Br, I or tosyl In N,N-dimethyl-formamide; paraffin oil at -10 - 20℃; for 12h; Stage #3: With hydrogenchloride In water 2 General procedure: Synthesis of the compounds A to L is carried out according to example 1 in that the corresponding alkyl iodides, alkyl bromides or alkyl tosylates were used. Yields were between 30 and 75% of the theoretical yield.A stirred solution of 13 g (0.0756 Mol) 1,2,3,4-tetrahydro-β-carboline, manufactured by tryptamine hydrochloride and glyoxylic acid as described by Ho and Walker (1988), and 2.6 g Pd/C (10%) in 600 ml of cumene were refluxed in a nitrogen atmosphere for 90 min. After addition of 100 ml of ethanol, the hot solution was filtrated, and the coal was extracted thrice by 30 ml of hot ethanol. The combined liquid fractions were concentrated, and the residues was crystallised in toluene to yield 10.5 g (82%) or norharman. Methylation at position 9 was performed as described in the literature (Ho B T, Mcisaac W M, Walker K E, Estevez V, J Pharm Sci 57: 269, 1968) yet with an improved reprocessing. One gram (5.95 mmol) of norharman was dissolved in 10 ml of dried DMF in a nitrogen atmosphere. After that, 0.36 g (14.9 mmol) of sodium hydride were added in form of a 60% dispersion in paraffin at 0° C. After cooling of the reaction mixture down to room temperature, this was cooled down to -10° C., and 0.84 g (5.95 mmol) iodomethane were added. After further stirring for 12 hours, one allowed the mixture to cool down to room temperature once again. All volatile ingredients were removed in reduced pressure. After that, 100 ml of water were added, and the mixture was extracted by 3×50 ml of CHCl3. The combined organic fractions were washed with 5×20 ml of water and were evaporated for drying. The residue was suspended in 100 ml 2 N hydrochloric acid. To separate the educt from the desired methylated product, ion pair exchange extraction of the HCl salt was performed in CHCl3 by a liquid/liquid extractor for two days. After removal of the solvent one yielded 0.7 g (64%) of yellow crystals of 9-methyl-β-carbolinium hydrochloride.[0098]Melting point: 295° C.; GC/MS of the free base: m/z=182 (100%), 167 (5%), 140 (10%), 127 (10%), 113 (5%), 91 (10%). 1H-NMR(HCl salt): δ (ppm) methanol d4, 250 MHz: 4.06 s, 3H, N-CH3; 7.28-7.35, dt, J=1.2; 6.8, 1H, H6; 7.58-7.70, m, 2H, H7, H8; 8.13-8.16, d, J=5.4, 1H, H4; 8.18-8.21, d, J=7.9, 1H H5; 8.31-8.33, d, J=5.4, 1H, H3; 8.89, s, 1H, H1.
  • 33
  • [ 244-63-3 ]
  • [ 446-52-6 ]
  • (2-fluorophenyl)(9H-pyrido[3,4-b]indol-1-yl)methanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% With tert.-butylhydroperoxide In water for 0.666667h; Microwave irradiation; Acidic conditions; Procedure for the microwave-assisted Minisci reaction: A mixture of β-carboline (3) (100 mg, 0.6 mmol), o-fluorobenzaldehyde (4) (3.5 g, 28 mmol), t-BuOOH (70% solution in H2O, 0.25 mL, 1.8 mmol), and AcOH (2.5 mL) was placed in a sealed 10 mL vial and irradiated using a Discover microwave synthesis system (CEM Corporation, www.cem.com) at 10 W for 40 min. The addition of t-BuOOH (70% solution in H2O, 0.25 mL, 1.8 mmol) and microwave irradiation was repeated until there was no starting material left (TLC monitoring). The mixture was poured into H2O (100 mL) and then neutralized with K2CO3 and extracted with EtOAc (3 × 50 mL). The combined organic layer was washed with brine (2 × 100 mL), dried over Na2SO4, and evaporated under reduced pressure. Compound 5 was isolated by flash column chromatography (EtOAc/hexanes 1:50) (172 mg, 65%) as yellow solid; mp 172-173 °C. IR (CHCl3) νmax: 3443, 3070, 3000, 1642, 1623, 1600, 1506, 1493, 1156, 669 cm-1; 1H NMR (400 MHz, C6D6) δ: 10.35 (br s, 1H, NH), 8.71 (dd, J1 = 8.9 Hz, J2 = 4.0 Hz, 2H), 8.52 (d, J = 4.9 Hz, 1H), 7.91 (d, J = 7.8 Hz, 1H), 7.64 (d, J = 4.9 Hz, 1H), 7.39 (dd, J1 = 8.2 Hz, J2 = 7.2 Hz, 1H), 7.22 (dd, J1 = 7.8 Hz, J2 = 7.2 Hz, 1H), 6.98 (t, J = 8.9 Hz, 2H), 6.89 (d, J = 8.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ: 193.5, 167.1, 163.7, 140.9, 137.9, 137.3, 136.1, 134.0, 133.9, 131.7, 129.3, 123.6, 121.8, 120.8, 118.5, 115.2, 114.9, 111.9; MS (EI) m/z = 290 (M+, 100), 262 (84), 167 (7), 145 (13), 140 (20), 123 (31), 95 (51). Anal. Calcd for C18H11FN2O: C, 74.48; H, 3.82; N, 9.65. Found: C, 74.52; H, 3.74; N, 9.55.
  • 34
  • 2,3,4,4a,9,9a-hexahydro-1H-beta-carboline [ No CAS ]
  • [ 244-63-3 ]
YieldReaction ConditionsOperation in experiment
91% With oxygen In ethanol; water at 20℃; for 12h; Irradiation;
With palladium on activated charcoal In para-xylene
  • 35
  • [ 244-63-3 ]
  • [ 1433878-31-9 ]
YieldReaction ConditionsOperation in experiment
84% With sodium hydride In N,N-dimethyl-formamide at 20℃; 5.2. General procedure for the preparation of 9-substituted β-carboline derivatives (2c-m) General procedure: A mixture of β-carbolines 1 (5 mmol) and anhydrous DMF (50 ml) was stirred at room temperature until clear, and then 60% NaH (0.3 g, 7.5 mmol) and alkyl halide (10-15 mmol) were added. The mixture was stirred at room temperature for 0.5-4 h. After completion of the reaction as indicated by TLC, the solution was poured into H2O (150 ml), and extracted with ethyl acetate. The combined organic phase was made acidic with concentrated hydrochloric acid. Upon removal of solvent, the residue was crystallized from acetone to afford yellow solid. The solid was dissolved in water and made basic with sodium bicarbonate, and the aqueous mixture extracted with ethyl acetate. The organic phase was washed with water and brine, then dried over anhydrous sodium sulfate, filtered and evaporated. The resulting oil was purified by a column chromatography, using a mixture of acetone and petroleum ether (1:4) as an eluent, to successfully afford the intermediates 2c-m in good yield.
  • 36
  • [ 244-63-3 ]
  • [ 94681-48-8 ]
YieldReaction ConditionsOperation in experiment
87% With sodium hydride In N,N-dimethyl-formamide at 20℃; 5.2. General procedure for the preparation of 9-substituted β-carboline derivatives (2c-m) General procedure: A mixture of β-carbolines 1 (5 mmol) and anhydrous DMF (50 ml) was stirred at room temperature until clear, and then 60% NaH (0.3 g, 7.5 mmol) and alkyl halide (10-15 mmol) were added. The mixture was stirred at room temperature for 0.5-4 h. After completion of the reaction as indicated by TLC, the solution was poured into H2O (150 ml), and extracted with ethyl acetate. The combined organic phase was made acidic with concentrated hydrochloric acid. Upon removal of solvent, the residue was crystallized from acetone to afford yellow solid. The solid was dissolved in water and made basic with sodium bicarbonate, and the aqueous mixture extracted with ethyl acetate. The organic phase was washed with water and brine, then dried over anhydrous sodium sulfate, filtered and evaporated. The resulting oil was purified by a column chromatography, using a mixture of acetone and petroleum ether (1:4) as an eluent, to successfully afford the intermediates 2c-m in good yield.
  • 37
  • [ 244-63-3 ]
  • [ 1433877-62-3 ]
YieldReaction ConditionsOperation in experiment
59% With sodium hydride In N,N-dimethyl-formamide at 20℃; 5.2. General procedure for the preparation of 9-substituted β-carboline derivatives (2c-m) General procedure: A mixture of β-carbolines 1 (5 mmol) and anhydrous DMF (50 ml) was stirred at room temperature until clear, and then 60% NaH (0.3 g, 7.5 mmol) and alkyl halide (10-15 mmol) were added. The mixture was stirred at room temperature for 0.5-4 h. After completion of the reaction as indicated by TLC, the solution was poured into H2O (150 ml), and extracted with ethyl acetate. The combined organic phase was made acidic with concentrated hydrochloric acid. Upon removal of solvent, the residue was crystallized from acetone to afford yellow solid. The solid was dissolved in water and made basic with sodium bicarbonate, and the aqueous mixture extracted with ethyl acetate. The organic phase was washed with water and brine, then dried over anhydrous sodium sulfate, filtered and evaporated. The resulting oil was purified by a column chromatography, using a mixture of acetone and petroleum ether (1:4) as an eluent, to successfully afford the intermediates 2c-m in good yield.
  • 38
  • [ 244-63-3 ]
  • [ 1448261-83-3 ]
YieldReaction ConditionsOperation in experiment
86% With sodium hydride In N,N-dimethyl-formamide at 20℃; 5.2. General procedure for the preparation of 9-substituted β-carboline derivatives (2c-m) General procedure: A mixture of β-carbolines 1 (5 mmol) and anhydrous DMF (50 ml) was stirred at room temperature until clear, and then 60% NaH (0.3 g, 7.5 mmol) and alkyl halide (10-15 mmol) were added. The mixture was stirred at room temperature for 0.5-4 h. After completion of the reaction as indicated by TLC, the solution was poured into H2O (150 ml), and extracted with ethyl acetate. The combined organic phase was made acidic with concentrated hydrochloric acid. Upon removal of solvent, the residue was crystallized from acetone to afford yellow solid. The solid was dissolved in water and made basic with sodium bicarbonate, and the aqueous mixture extracted with ethyl acetate. The organic phase was washed with water and brine, then dried over anhydrous sodium sulfate, filtered and evaporated. The resulting oil was purified by a column chromatography, using a mixture of acetone and petroleum ether (1:4) as an eluent, to successfully afford the intermediates 2c-m in good yield.
  • 39
  • [ 244-63-3 ]
  • [ 1313283-35-0 ]
YieldReaction ConditionsOperation in experiment
63% With sodium hydride In N,N-dimethyl-formamide at 20℃; 5.2. General procedure for the preparation of 9-substituted β-carboline derivatives (2c-m) General procedure: A mixture of β-carbolines 1 (5 mmol) and anhydrous DMF (50 ml) was stirred at room temperature until clear, and then 60% NaH (0.3 g, 7.5 mmol) and alkyl halide (10-15 mmol) were added. The mixture was stirred at room temperature for 0.5-4 h. After completion of the reaction as indicated by TLC, the solution was poured into H2O (150 ml), and extracted with ethyl acetate. The combined organic phase was made acidic with concentrated hydrochloric acid. Upon removal of solvent, the residue was crystallized from acetone to afford yellow solid. The solid was dissolved in water and made basic with sodium bicarbonate, and the aqueous mixture extracted with ethyl acetate. The organic phase was washed with water and brine, then dried over anhydrous sodium sulfate, filtered and evaporated. The resulting oil was purified by a column chromatography, using a mixture of acetone and petroleum ether (1:4) as an eluent, to successfully afford the intermediates 2c-m in good yield.
  • 40
  • [ 244-63-3 ]
  • [ 116524-14-2 ]
YieldReaction ConditionsOperation in experiment
With sodium hydride In N,N-dimethyl-formamide at 20℃; 5.2. General procedure for the preparation of 9-substituted β-carboline derivatives (2c-m) A mixture of β-carbolines 1 (5 mmol) and anhydrous DMF (50 ml) was stirred at room temperature until clear, and then 60% NaH (0.3 g, 7.5 mmol) and alkyl halide (10-15 mmol) were added. The mixture was stirred at room temperature for 0.5-4 h. After completion of the reaction as indicated by TLC, the solution was poured into H2O (150 ml), and extracted with ethyl acetate. The combined organic phase was made acidic with concentrated hydrochloric acid. Upon removal of solvent, the residue was crystallized from acetone to afford yellow solid. The solid was dissolved in water and made basic with sodium bicarbonate, and the aqueous mixture extracted with ethyl acetate. The organic phase was washed with water and brine, then dried over anhydrous sodium sulfate, filtered and evaporated. The resulting oil was purified by a column chromatography, using a mixture of acetone and petroleum ether (1:4) as an eluent, to successfully afford the intermediates 2c-m in good yield.
  • 41
  • [ 244-63-3 ]
  • [ 21373-42-2 ]
YieldReaction ConditionsOperation in experiment
With sodium hydride In N,N-dimethyl-formamide at 20℃; 5.2. General procedure for the preparation of 9-substituted β-carboline derivatives (2c-m) General procedure: A mixture of β-carbolines 1 (5 mmol) and anhydrous DMF (50 ml) was stirred at room temperature until clear, and then 60% NaH (0.3 g, 7.5 mmol) and alkyl halide (10-15 mmol) were added. The mixture was stirred at room temperature for 0.5-4 h. After completion of the reaction as indicated by TLC, the solution was poured into H2O (150 ml), and extracted with ethyl acetate. The combined organic phase was made acidic with concentrated hydrochloric acid. Upon removal of solvent, the residue was crystallized from acetone to afford yellow solid. The solid was dissolved in water and made basic with sodium bicarbonate, and the aqueous mixture extracted with ethyl acetate. The organic phase was washed with water and brine, then dried over anhydrous sodium sulfate, filtered and evaporated. The resulting oil was purified by a column chromatography, using a mixture of acetone and petroleum ether (1:4) as an eluent, to successfully afford the intermediates 2c-m in good yield.
  • 42
  • [ 244-63-3 ]
  • [ 1313283-31-6 ]
YieldReaction ConditionsOperation in experiment
79% With sodium hydride In N,N-dimethyl-formamide at 20℃; 5.2. General procedure for the preparation of 9-substituted β-carboline derivatives (2c-m) General procedure: A mixture of β-carbolines 1 (5 mmol) and anhydrous DMF (50 ml) was stirred at room temperature until clear, and then 60% NaH (0.3 g, 7.5 mmol) and alkyl halide (10-15 mmol) were added. The mixture was stirred at room temperature for 0.5-4 h. After completion of the reaction as indicated by TLC, the solution was poured into H2O (150 ml), and extracted with ethyl acetate. The combined organic phase was made acidic with concentrated hydrochloric acid. Upon removal of solvent, the residue was crystallized from acetone to afford yellow solid. The solid was dissolved in water and made basic with sodium bicarbonate, and the aqueous mixture extracted with ethyl acetate. The organic phase was washed with water and brine, then dried over anhydrous sodium sulfate, filtered and evaporated. The resulting oil was purified by a column chromatography, using a mixture of acetone and petroleum ether (1:4) as an eluent, to successfully afford the intermediates 2c-m in good yield.
  • 43
  • [ 244-63-3 ]
  • [ 1313283-37-2 ]
YieldReaction ConditionsOperation in experiment
73% With sodium hydride In N,N-dimethyl-formamide at 20℃; 5.2. General procedure for the preparation of 9-substituted β-carboline derivatives (2c-m) General procedure: A mixture of β-carbolines 1 (5 mmol) and anhydrous DMF (50 ml) was stirred at room temperature until clear, and then 60% NaH (0.3 g, 7.5 mmol) and alkyl halide (10-15 mmol) were added. The mixture was stirred at room temperature for 0.5-4 h. After completion of the reaction as indicated by TLC, the solution was poured into H2O (150 ml), and extracted with ethyl acetate. The combined organic phase was made acidic with concentrated hydrochloric acid. Upon removal of solvent, the residue was crystallized from acetone to afford yellow solid. The solid was dissolved in water and made basic with sodium bicarbonate, and the aqueous mixture extracted with ethyl acetate. The organic phase was washed with water and brine, then dried over anhydrous sodium sulfate, filtered and evaporated. The resulting oil was purified by a column chromatography, using a mixture of acetone and petroleum ether (1:4) as an eluent, to successfully afford the intermediates 2c-m in good yield.
  • 44
  • [ 244-63-3 ]
  • [ 1433877-48-5 ]
YieldReaction ConditionsOperation in experiment
70% With sodium hydride In N,N-dimethyl-formamide at 20℃; 5.2. General procedure for the preparation of 9-substituted β-carboline derivatives (2c-m) General procedure: A mixture of β-carbolines 1 (5 mmol) and anhydrous DMF (50 ml) was stirred at room temperature until clear, and then 60% NaH (0.3 g, 7.5 mmol) and alkyl halide (10-15 mmol) were added. The mixture was stirred at room temperature for 0.5-4 h. After completion of the reaction as indicated by TLC, the solution was poured into H2O (150 ml), and extracted with ethyl acetate. The combined organic phase was made acidic with concentrated hydrochloric acid. Upon removal of solvent, the residue was crystallized from acetone to afford yellow solid. The solid was dissolved in water and made basic with sodium bicarbonate, and the aqueous mixture extracted with ethyl acetate. The organic phase was washed with water and brine, then dried over anhydrous sodium sulfate, filtered and evaporated. The resulting oil was purified by a column chromatography, using a mixture of acetone and petroleum ether (1:4) as an eluent, to successfully afford the intermediates 2c-m in good yield.
  • 45
  • [ 244-63-3 ]
  • [ 2521-07-5 ]
YieldReaction ConditionsOperation in experiment
80% Stage #1: betacarboline With sodium hydride In N,N-dimethyl-formamide at 20℃; for 1h; Stage #2: methyl halide In N,N-dimethyl-formamide at 20℃; for 12h; 4-N-Substituted-β-carbolines (13a-c) General procedure: To a solution of β-carboline 12a-c (1 mmol) in DMF (20 mL) was added sodium hydride (3 mmol) portion wise and the resulting reaction mixture was stirred at room temperature for 1 h. Next, a solution of alkyl halide (1.2 mmol) in DMF (2 mL) was added drop wise to reaction mixture and stirred for 12 h at room temperature. Upon completion of reaction, the contents were poured over crushed ice (100 gm) and extracted with DCM (3 × 30 mL), dried and removed the excess solvent under vaccuo. The residue so obtained was purified by column chromatography using ethyl acetate:hexane (1:1) as an eluent to afford N-alkylated β-carbolines 13a-c in 77-85% yields .
With sodium hydride In N,N-dimethyl-formamide at 20℃;
  • 46
  • [ 244-63-3 ]
  • [ 1433877-55-4 ]
YieldReaction ConditionsOperation in experiment
75% With sodium hydride In N,N-dimethyl-formamide at 20℃; 5.2. General procedure for the preparation of 9-substituted β-carboline derivatives (2c-m) General procedure: A mixture of β-carbolines 1 (5 mmol) and anhydrous DMF (50 ml) was stirred at room temperature until clear, and then 60% NaH (0.3 g, 7.5 mmol) and alkyl halide (10-15 mmol) were added. The mixture was stirred at room temperature for 0.5-4 h. After completion of the reaction as indicated by TLC, the solution was poured into H2O (150 ml), and extracted with ethyl acetate. The combined organic phase was made acidic with concentrated hydrochloric acid. Upon removal of solvent, the residue was crystallized from acetone to afford yellow solid. The solid was dissolved in water and made basic with sodium bicarbonate, and the aqueous mixture extracted with ethyl acetate. The organic phase was washed with water and brine, then dried over anhydrous sodium sulfate, filtered and evaporated. The resulting oil was purified by a column chromatography, using a mixture of acetone and petroleum ether (1:4) as an eluent, to successfully afford the intermediates 2c-m in good yield.
  • 47
  • [ 244-63-3 ]
  • [ 752213-27-7 ]
YieldReaction ConditionsOperation in experiment
Stage #1: betacarboline With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: In N,N-dimethyl-formamide Stage #3: With hydrogenchloride In diethyl ether; isopropyl alcohol 6.2. Synthesis of indolo-N-alkyl-carboline derivatives (2, 6-10): General procedure 1 General procedure: A solution of 4 mmol carboline (12 or 14) and 4.4 mmol of NaH in DMF was stirred at room temperature for 30 min. After addition of 4.4 mmol of corresponding alkyl halide the solution was stirred for another 4-16 h. The conversion was monitored by TLC and GC/MS. When no further reaction was observed the solution was poured into iced water extracted with dichloromethane and purified by column chromatography and was subsequently converted into its HCl salt in 2-propanol with ethereal HCl.
  • 48
  • [ 244-63-3 ]
  • [ 103-63-9 ]
  • [ 94258-13-6 ]
YieldReaction ConditionsOperation in experiment
Stage #1: betacarboline With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: 1-phenyl-2-bromoethane In N,N-dimethyl-formamide for 16h; 6.2. Synthesis of indolo-N-alkyl-carboline derivatives (2, 6-10): General procedure 1 General procedure: A solution of 4 mmol carboline (12 or 14) and 4.4 mmol of NaH in DMF was stirred at room temperature for 30 min. After addition of 4.4 mmol of corresponding alkyl halide the solution was stirred for another 4-16 h. The conversion was monitored by TLC and GC/MS. When no further reaction was observed the solution was poured into iced water extracted with dichloromethane and purified by column chromatography and was subsequently converted into its HCl salt in 2-propanol with ethereal HCl.
  • 49
  • [ 244-63-3 ]
  • [ 106-96-7 ]
  • 9-prop-2-ynylpyrido[3,4-b]indole [ No CAS ]
YieldReaction ConditionsOperation in experiment
38% Stage #1: betacarboline With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: propargyl bromide In N,N-dimethyl-formamide for 4h; 6.2. Synthesis of indolo-N-alkyl-carboline derivatives (2, 6-10): General procedure 1 General procedure: A solution of 4 mmol carboline (12 or 14) and 4.4 mmol of NaH in DMF was stirred at room temperature for 30 min. After addition of 4.4 mmol of corresponding alkyl halide the solution was stirred for another 4-16 h. The conversion was monitored by TLC and GC/MS. When no further reaction was observed the solution was poured into iced water extracted with dichloromethane and purified by column chromatography and was subsequently converted into its HCl salt in 2-propanol with ethereal HCl.
  • 50
  • [ 244-63-3 ]
  • [ 17954-81-3 ]
  • 4-(3-(9H-pyrido[3,4-b]indol-9-yl)propoxy)benzaldehyde [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% Stage #1: betacarboline With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: 4-(3-bromopropoxy)benzaldehyde In N,N-dimethyl-formamide at 20℃; for 24h; Synthesis of 4-(3-(9H-pyrido[3,4-b]indol-9-yl)propoxy)benzaldehyde (5) A mixture of compound 2 (336mg, 2.0mmol), NaH (144mg, 6.0mmol) and dry N,N-dimethylformamide (DMF, 20mL) was stirred in an ice bath for 30min, and then compound 4 (532mg, 2.2mmol) was added to the solution. After reacting for 24h at RT and extraction with dichloromethane (DCM), the organic phase was dried over Na2SO4. The solvent was removed, and the residue was purified by PTLC using DCM/ethyl acetate/triethylamine (20:1.5:0.2, v/v/v) as the eluent, to give 541mg (82%) of compound 5 as a yellow solid. Melting point: 107-108°C. 1H NMR (500MHz, CDCl3) δ: 9.90 (s, 1H), 8.94 (s, 1H), 8.49 (d, J=5Hz, 1H), 8.16 (d, J=8Hz, 1H), 7.98 (d, J=5Hz, 1H), 7.84 (d, J=8.5Hz, 2H), 7.48-7.54 (m, 2H), 7.30 (t, J=5Hz, 1H), 6.97 (d, J=5Hz, 2H), 4.67 (t, J=5Hz, 2H), 4.00 (t, J=5Hz, 2H), 2.43-2.48 (m, 2H). 13CC NMR (125MHz, CDCl3) δ: 190.78, 163.39, 141.20, 139.20, 136.44, 132.05, 131.91, 130.25, 128.52, 121.98, 121.17, 119.88, 114.73, 114.63, 109.32, 64.70, 39.65, 28.66. EI-MS: m/z=331.15 (calculated 330.14 for C21H18N2O2).
  • 51
  • [ 58911-02-7 ]
  • [ 244-63-3 ]
YieldReaction ConditionsOperation in experiment
95% With 5 mol% Pd/C; lithium carbonate In ethanol at 150℃; for 1h; Sealed tube; Microwave irradiation;
53% With lithium carbonate; silver carbonate In N,N-dimethyl-formamide for 19h; Reflux; General Procedure for the Oxidation of Tetrahydro-β-Carboline salts with Ag2CO3 General procedure: 1-Phenyl-2,3,4,9-tetrahydro-1H-β-carboline HCl salt (142.0 mg, 0.5 mmol), Ag2CO3 (276.0 mg, 1.0 mmol), Li2CO3 (74.0 mg, 1.0 mmol), and DMF (10 mL, 0.1M) were added to a 50 mL round bottom flask containing a stir bar. A condenser was attached, and the solution was heated at reflux with stirring for 16 hours. Once the starting material was consumed (as shown by TLC in 10:1 CH2Cl2:MeOH visualized with CAM stain), the solvent was removed using a rotatory evaporator. The crude product was loaded onto diatomaceous earth and subsequently purified by silica column with 3:1 hexanes:EtOAc as the eluent. Product separation was monitored by TLC (3:1 hexanes:EtOAc, visualized under a UV lamp at 365 nm and 254 nm). The purified product was obtained as a light tan solid (122 mg, 70%).
  • 52
  • [ 7681-65-4 ]
  • [ 244-63-3 ]
  • [ 603-35-0 ]
  • (chlorido)(norharmane)bis(triphenylphosphane)copper(I) [ No CAS ]
YieldReaction ConditionsOperation in experiment
78% Stage #1: copper(l) iodide; triphenylphosphine In acetonitrile at 80℃; for 1h; Stage #2: betacarboline In methanol; acetonitrile for 4h; 2.2.1. Synthesis of [CuI(PPh3)2(Hnor)] (1) CuI (0.095 g, 0.05 mmol) and PPh3 (0.262 g, 0.10 mmol) in 10 ml of MeCN were stirred for 1 h at 80 °C to get a clear solution. To the reaction mixture, a solution of Hnor (0.082 g, 0.05 mmol) in methanol (5 mL) was added dropwise and left on stirring for 4 h. Then the mixture was filtered, and a colorless clear solution was obtained, which was left for slow evaporation leading to crystallization at room temperature. After a few days white crystals were obtained that were suitable for a single-crystal X-ray diffraction analysis. (Yield: 78%). Anal. Calc. for [CuI(PPh3)2(Hnor)]: C, 63.91; H, 4.34;N, 3.17. Found: C, 64.11; H, .23; N, 2.76%. m.p. = 202 °C. IR (KBr, cm-1): 3446, 3142, 3047, 1627, 1478, 1452, 1434, 1248, 740,694, 514. 1H NMR (DMSO-d6): δ (ppm) = 11.68 (1H, NH); 8.99 (s, 1H, H1); 8.26-8.21 (m, 2H, H7 and H5); 8.08-8.07 (d, 2H, H7); 7.60-7.53 (m, 3H, H6, H3 and H4); 7.40-7.21 (m, 30H, PPh3). 13C NMR (DMSO-d6; ppm): 140.7 (C1, Hnor), 138.2 (C11, Hnor), 135.7 (C3, Hnor), 134.4 (C12, C18, C24, C30, C36, C42, PPh3) 133.5 (C8, Hnor),133.3 (C2, Hnor), 129.6, 128.4 (Cs, PPH3) 127.6 (C10, Hnor), 121.8 (C6, Hnor), 120.3 (C7, Hnor), 119.4 (C5, Hnor), 114.8 (C4, Hnor), 111.9 (C9, Hnor). 31P NMR (DMSO-d6; ppm): -6.5 ppm.
  • 53
  • [ 244-63-3 ]
  • [ 603-35-0 ]
  • [ 7787-70-4 ]
  • [CuI(PPh3)2(9H-pyrido[3,4-b]indole)Br] [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% General procedure: CuI (0.095 g, 0.05 mmol) and PPh3 (0.262 g, 0.10 mmol) in 10 ml of MeCN were stirred for 1 h at 80 C to get a clear solution. To the reaction mixture, a solution of Hnor (0.082 g, 0.05 mmol) in methanol (5 mL) was added dropwise and left on stirring for 4 h. Then the mixture was filtered, and a colorless clear solution was obtained, which was left for slow evaporation leading to crystallization at room temperature. After a few days white crystals were obtained that were suitable for a single-crystal X-ray diffraction analysis.
  • 54
  • [ 244-63-3 ]
  • [ 603-35-0 ]
  • copper(l) chloride [ No CAS ]
  • [CuI(PPh3)2(9H-pyrido[3,4-b]indole)Cl] [ No CAS ]
YieldReaction ConditionsOperation in experiment
84% Stage #1: triphenylphosphine; copper(l) chloride In acetonitrile at 80℃; for 1h; Stage #2: betacarboline In methanol; acetonitrile for 4h; 2.2.1. Synthesis of [CuI(PPh3)2(Hnor)] (1) General procedure: CuI (0.095 g, 0.05 mmol) and PPh3 (0.262 g, 0.10 mmol) in 10 ml of MeCN were stirred for 1 h at 80 °C to get a clear solution. To the reaction mixture, a solution of Hnor (0.082 g, 0.05 mmol) in methanol (5 mL) was added dropwise and left on stirring for 4 h. Then the mixture was filtered, and a colorless clear solution was obtained, which was left for slow evaporation leading to crystallization at room temperature. After a few days white crystals were obtained that were suitable for a single-crystal X-ray diffraction analysis.
  • 55
  • [ 244-63-3 ]
  • C20H12Br2 [ No CAS ]
  • C31H19BrN2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
49% With 18-crown-6 ether; copper; potassium carbonate In nitrobenzene at 200℃; II.7.2 Sub 2-II-107 synthesis 9H-pyrido [3,4-b] indole (14.97g, 89mmol) was dissolved in nitrobenzene to a round bottom flask, Sub 2-I-107 (55.02g, 133.5mmol), 18-crown-6 (2.35g, 8.9mmol), K2CO3 (the addition of 12.3g, 89mmol), Cu (5.66g, 89mmol) and the resulting mixture was stirred at 200 C. After completion of reaction nitrobenzene was removed by distillation and extracted with water and CH2Cl2. The resulting compound and the organic layer was dried over MgSO4 and concentrated to silicagel column and the product 21.78g (yield: 49%) was obtained.
  • 56
  • [ 624-28-2 ]
  • [ 244-63-3 ]
  • C16H10BrN3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
55.7% With copper(l) iodide; 1,10-Phenanthroline; caesium carbonate In 1,4-dioxane at 100℃; Inert atmosphere; 12 One 100 mL Flask in β-caboline 500 mg (2.97 mmol), 2,5-dibromopyridine 1.06 g (4.46 mmol) and CuI 283 mg (1.49 mmol), CS2CO3 1.94 g (5.940 mmol) and 1,10-phenanthroline 535 mg (2.975 mmol )And the mixture was dissolved in 1,4-dioxane 15 mL under a nitrogen atmosphere It was stirred under reflux at 100 . After cooling to room temperature the reaction was terminated, and the MC 20 mL into the mixture the solid was filtered and concentrated under reduced pressure of the filtrate. Purification of the resulting compound by silica gel column chromatography to give compound as a pale yellow solid (intermediate (14)) 537mg (yield: 55.7%) was obtained
  • 57
  • [ 244-63-3 ]
  • C37H22BrN [ No CAS ]
  • C48H29N3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
50.5% With copper(l) iodide; 1,10-Phenanthroline; caesium carbonate In 1,4-dioxane at 100℃; Inert atmosphere; 27 One 25 mL Flask in β-caboline 150 mg (0.89 mmol), Intermediate Compound (6) 650 mg (1.16 mmol) and CuI 85mg (0.45 mmol), CS2CO3 580 mg (1.78 mmol) and 1,10-phenanthroline 160 mg (0.89 mmol)The insert was dissolved in 1,4-dioxane under a nitrogen atmosphere 9 mL It was stirred under reflux at 100 . After cooling to room temperature the reaction was terminated, and the MC 20 mL into the mixture the solid was filtered and concentrated under reduced pressure of the filtrate. Purification of the resulting compound by silica gel column chromatography to give the compound as a yellow solid (5-27, KJ-05-10), 291 mg (yield: 50.5%) was obtained.
  • 58
  • [ 244-63-3 ]
  • [ 187086-32-4 ]
  • C43H26N2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
19% With copper(l) iodide; 1,10-Phenanthroline; caesium carbonate; In N,N-dimethyl-formamide; at 140℃;Inert atmosphere; One 100 mL Flask in intermediate (2) 0.5 g (1.03 mmol), beta-caboline 0.26 g (1.55 mmol) and CuI 80mg (0.52 mmol), CS2CO3 0.67 g (2.06 mmol) and 1,10-phenanthroline 0.186 g (1.03 mmol) of insert was stirred under reflux at 140 Dimethylformamide was dissolved in 5 mL under a nitrogen atmosphere. After cooling to room temperature the reaction was terminated, and the MC 20 mL into the mixture the solid was filtered and concentrated under reduced pressure of the filtrate. Purification of the resulting compound was purified by silica gel column chromatography to obtain a compound (5-6, HSB-04-037) 0.11 g (Yield: 19%) of a white solid was obtained.
  • 59
  • [ 244-63-3 ]
  • C26H16IN3 [ No CAS ]
  • C37H23N5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
5% With copper(l) iodide; 1,10-Phenanthroline; caesium carbonate In N,N-dimethyl-formamide at 120 - 130℃; for 12h; 4 Synthesis of Compound (4-4) One 100 mLThe flask Intermediate (1) (0.5 g, 1.005 mmol), beta -carboline (b-carboline) 0.2 g (1.105mmol), CuI 24 mg (0.126 mmol), 1,10 phenanthroline (1,10 phenanthroline) 45mg (0.251 mmol), cesium carbonate (cesium carbonate, Cs2CO3) 0.7 g (2.010 mmol) and dimethylformamide (dimethylformamide, DMF) (40 mL) and mixed, and then,stirred for 12 hours at 120 ~ 130°C. The reaction was cooled to room temperature and then terminated and purified by silica gel column chromatography to give compound (4-4) 27 mg (Yield: 5%) of a white solid was obtained.
  • 60
  • [ 244-63-3 ]
  • C26H16IN3 [ No CAS ]
  • C37H23N5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
7% With copper(l) iodide; 1,10-Phenanthroline; caesium carbonate In N,N-dimethyl-formamide at 120 - 130℃; for 12h; 24 Synthesis of Compound (4-24) One 100 mLThe flask Intermediate (2) (0.5 g, 1.005 mmol), beta-carboline(-b-carboline)0.2 g (1.105mmol), CuI 24 mg (0.126 mmol), 1,10 phenanthroline (1,10 phenanthroline) 45mg (0.251 mmol), cesium carbonate (cesium carbonate, Cs2CO3) 0.7 g (2.010 mmol) and dimethylformamide (dimethylformamide, DMF) (40 mL) and mixed, and then,stirred for 12 hours at 120 ~ 130°C. The reaction was cooled to room temperature and then terminated and purified by silica gel column chromatography to give compound (4-24) 38 mg (Yield: 7 %) of a white solid was obtained.
  • 61
  • [ 144981-86-2 ]
  • [ 244-63-3 ]
  • C37H26N4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
37% With potassium phosphate; copper(l) iodide; trans-1,2-Diaminocyclohexane In 1,4-dioxane for 12h; Reflux; 4 4. Synthesis of Compound (FL-4) Example 8 As shown in Scheme 8 above, 2.5 g (5.59 mmol) of compound X4, 2.07 g (12.307 mmol) of carboline, 852 mg (4.48 mmol) of copper iodide (CuI) and potassium tribasicterinate (K3PO4) G (33.57 mmol) of trans-1,2-cyclohexanediamine and 0.54 mL (4.48 mmol) of trans-1,2-cyclohexanediamine were dissolved in 1,4-dioxane and refluxed for 12 hours. After completion of the reaction, the solvent was distilled off under reduced pressure, and the residue was subjected to column chromatography using a solvent mixture of n-hexane and ethyl acetate (3: 1), and the solution was distilled under reduced pressure to obtain methylene chloride and petroleum And recrystallized in a solvent of petroleum ether to obtain 1.08 g (yield 37%) of the compound FL-4.
  • 62
  • [ 244-63-3 ]
  • [ 141-76-4 ]
  • 2-(2-carboxyethyl)-norharmanium [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide In methanol at 20℃; Darkness;
  • 63
  • [ 244-63-3 ]
  • [ 155666-33-4 ]
  • 2-hydroxy-3-Methoxy-7,8-Dehydrorutaecarpine [ No CAS ]
  • 64
  • [ 244-63-3 ]
  • [ 1882-71-9 ]
  • 3-methoxy-7,8-dehydrorutaecarpine [ No CAS ]
  • 65
  • [ 244-63-3 ]
  • [ 70-11-1 ]
  • 2-(2-oxo-2-phenylethyl)-9H-pyrido[3,4-b]indol-2-ium bromide [ No CAS ]
YieldReaction ConditionsOperation in experiment
89% In ethanol at 80℃; Microwave irradiation; 6. β-Carbolinium bromides (16a-t) General procedure: β-Carboline 12 or 13 (0.1 g, 0.6 mmol), 1-aryl-2-bromoethanone 15 (0.72 mmol) and ethanol (3 mL) were taken in 10 mL microwave (MW) vial. The resulting mixture was irradiated in focused MW oven for 20 min at 80 °C. Upon completion of reaction as indicated by TLC, ethanol was evaporated in vaccuo and the residue so obtained was precipitated with ethyl acetate. The obtained solid was filtered and washed with ethyl acetate (2 x 10 mL) to afford 16a-t in 75-92% yields. 2-(2-Oxo-2-phenylethyl)-9H-pyrido[3,4-b]indol-2-ium bromide (16a) Yellow solid; Yield: 89%; mp: 225-226 °C; IR (KBr, v, cm-1): 3418, 3009, 2955, 2908, 2862, 1697, 1643, 1520, 1450, 1381, 1342, 1227, 903, 764, 687; 1H NMR (400 MHz, DMSO-d6) δ 13.05 (s, 1H), 9.46 (s, 1H), 8.94 (d, J = 6.3 Hz, 1H), 8.69 (d, J = 6.3 Hz, 1H), 8.56 (d, J = 8.0 Hz, 1H), 8.13 (d, J = 7.5 Hz, 2H), 7.86-7.80 (m, 3H), 7.71-7.68 (m, 2H), 7.58-7.43 (m, 1H), 6.65 (s, 2H); 13C NMR (100 MHz, DMSO-d6) δ 192.0, 144.7, 135.1, 134.5, 134.2, 133.0, 132.7, 131.5, 129.6, 128.7, 124.2, 122.2, 119.6, 118.0, 113.6, 66.5; Anal. RP-HPLC tR = 2.650 min, purity 98.02%; MS (ESI+) calcd for C19H15BrN2O [M + H]+, 367.04; found 367.03; HRMS (ESI+) calcd for C19H15N2O+ [M-Br]+, 287.1179; found, 287.1176.
  • 66
  • [ 244-63-3 ]
  • [ 619-41-0 ]
  • 2-(2-oxo-2-(p-tolyl)ethyl)-9H-pyrido[3,4-b]indol-2-ium bromide [ No CAS ]
YieldReaction ConditionsOperation in experiment
91% In ethanol at 80℃; Microwave irradiation; 6. β-Carbolinium bromides (16a-t) General procedure: β-Carboline 12 or 13 (0.1 g, 0.6 mmol), 1-aryl-2-bromoethanone 15 (0.72 mmol) and ethanol (3 mL) were taken in 10 mL microwave (MW) vial. The resulting mixture was irradiated in focused MW oven for 20 min at 80 °C. Upon completion of reaction as indicated by TLC, ethanol was evaporated in vaccuo and the residue so obtained was precipitated with ethyl acetate. The obtained solid was filtered and washed with ethyl acetate (2 x 10 mL) to afford 16a-t in 75-92% yields.
  • 67
  • [ 244-63-3 ]
  • [ 2632-13-5 ]
  • 2-(2-(4-methoxyphenyl)-2-oxoethyl)-9H-pyrido[3,4-b]indol-2-ium bromide [ No CAS ]
YieldReaction ConditionsOperation in experiment
91% In ethanol at 80℃; Microwave irradiation; 6. β-Carbolinium bromides (16a-t) General procedure: β-Carboline 12 or 13 (0.1 g, 0.6 mmol), 1-aryl-2-bromoethanone 15 (0.72 mmol) and ethanol (3 mL) were taken in 10 mL microwave (MW) vial. The resulting mixture was irradiated in focused MW oven for 20 min at 80 °C. Upon completion of reaction as indicated by TLC, ethanol was evaporated in vaccuo and the residue so obtained was precipitated with ethyl acetate. The obtained solid was filtered and washed with ethyl acetate (2 x 10 mL) to afford 16a-t in 75-92% yields.
  • 68
  • [ 244-63-3 ]
  • [ 1835-02-5 ]
  • 2-(2-(3,4-dimethoxyphenyl)-2-oxoethyl)-9H-pyrido[3,4-b]indol-2-ium bromide [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% In ethanol at 80℃; Microwave irradiation; 6. β-Carbolinium bromides (16a-t) General procedure: β-Carboline 12 or 13 (0.1 g, 0.6 mmol), 1-aryl-2-bromoethanone 15 (0.72 mmol) and ethanol (3 mL) were taken in 10 mL microwave (MW) vial. The resulting mixture was irradiated in focused MW oven for 20 min at 80 °C. Upon completion of reaction as indicated by TLC, ethanol was evaporated in vaccuo and the residue so obtained was precipitated with ethyl acetate. The obtained solid was filtered and washed with ethyl acetate (2 x 10 mL) to afford 16a-t in 75-92% yields.
  • 69
  • [ 244-63-3 ]
  • [ 51490-01-8 ]
  • 2-(2-oxo-2-(3,4,5-trimethoxyphenyl)ethyl)-9H-pyrido[3,4-b]indol-2-ium bromide [ No CAS ]
YieldReaction ConditionsOperation in experiment
84% In ethanol at 80℃; Microwave irradiation; 6. β-Carbolinium bromides (16a-t) General procedure: β-Carboline 12 or 13 (0.1 g, 0.6 mmol), 1-aryl-2-bromoethanone 15 (0.72 mmol) and ethanol (3 mL) were taken in 10 mL microwave (MW) vial. The resulting mixture was irradiated in focused MW oven for 20 min at 80 °C. Upon completion of reaction as indicated by TLC, ethanol was evaporated in vaccuo and the residue so obtained was precipitated with ethyl acetate. The obtained solid was filtered and washed with ethyl acetate (2 x 10 mL) to afford 16a-t in 75-92% yields.
  • 70
  • [ 244-63-3 ]
  • [ 99-73-0 ]
  • 2-(2-(4-bromophenyl)-2-oxoethyl)-9H-pyrido[3,4-b]indol-2-ium bromide [ No CAS ]
YieldReaction ConditionsOperation in experiment
92% In ethanol at 80℃; Microwave irradiation; 6. β-Carbolinium bromides (16a-t) General procedure: β-Carboline 12 or 13 (0.1 g, 0.6 mmol), 1-aryl-2-bromoethanone 15 (0.72 mmol) and ethanol (3 mL) were taken in 10 mL microwave (MW) vial. The resulting mixture was irradiated in focused MW oven for 20 min at 80 °C. Upon completion of reaction as indicated by TLC, ethanol was evaporated in vaccuo and the residue so obtained was precipitated with ethyl acetate. The obtained solid was filtered and washed with ethyl acetate (2 x 10 mL) to afford 16a-t in 75-92% yields.
  • 71
  • [ 244-63-3 ]
  • [ 613-54-7 ]
  • 2-(2-(naphthalen-2-yl)-2-oxoethyl)-9H-pyrido[3,4-b]indol-2-ium bromide [ No CAS ]
YieldReaction ConditionsOperation in experiment
87% In ethanol at 80℃; Microwave irradiation; 6. β-Carbolinium bromides (16a-t) General procedure: β-Carboline 12 or 13 (0.1 g, 0.6 mmol), 1-aryl-2-bromoethanone 15 (0.72 mmol) and ethanol (3 mL) were taken in 10 mL microwave (MW) vial. The resulting mixture was irradiated in focused MW oven for 20 min at 80 °C. Upon completion of reaction as indicated by TLC, ethanol was evaporated in vaccuo and the residue so obtained was precipitated with ethyl acetate. The obtained solid was filtered and washed with ethyl acetate (2 x 10 mL) to afford 16a-t in 75-92% yields.
  • 72
  • [ 15109-94-1 ]
  • [ 244-63-3 ]
  • 2-(2-(furan-2-yl)-2-oxoethyl)-9H-pyrido[3,4-b]indol-2-ium bromide [ No CAS ]
YieldReaction ConditionsOperation in experiment
93% In ethanol at 80℃; Microwave irradiation; 6. β-Carbolinium bromides (16a-t) General procedure: β-Carboline 12 or 13 (0.1 g, 0.6 mmol), 1-aryl-2-bromoethanone 15 (0.72 mmol) and ethanol (3 mL) were taken in 10 mL microwave (MW) vial. The resulting mixture was irradiated in focused MW oven for 20 min at 80 °C. Upon completion of reaction as indicated by TLC, ethanol was evaporated in vaccuo and the residue so obtained was precipitated with ethyl acetate. The obtained solid was filtered and washed with ethyl acetate (2 x 10 mL) to afford 16a-t in 75-92% yields.
  • 73
  • [ 10531-41-6 ]
  • [ 244-63-3 ]
  • 2-(2-oxo-2-(thiophen-2-yl)ethyl)-9H-pyrido[3,4-b]indol-2-ium bromide [ No CAS ]
YieldReaction ConditionsOperation in experiment
91% In ethanol at 80℃; Microwave irradiation; 6. β-Carbolinium bromides (16a-t) General procedure: β-Carboline 12 or 13 (0.1 g, 0.6 mmol), 1-aryl-2-bromoethanone 15 (0.72 mmol) and ethanol (3 mL) were taken in 10 mL microwave (MW) vial. The resulting mixture was irradiated in focused MW oven for 20 min at 80 °C. Upon completion of reaction as indicated by TLC, ethanol was evaporated in vaccuo and the residue so obtained was precipitated with ethyl acetate. The obtained solid was filtered and washed with ethyl acetate (2 x 10 mL) to afford 16a-t in 75-92% yields.
  • 74
  • [ 244-63-3 ]
  • 9-(4-chlorobenzyl)-9H-pyrido[3,4-b]indole [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% Stage #1: betacarboline With sodium hydride In N,N-dimethyl-formamide at 20℃; for 1h; Stage #2: 4-chlorobenzyl halide In N,N-dimethyl-formamide at 20℃; for 12h; 4-N-Substituted-β-carbolines (13a-c) General procedure: To a solution of β-carboline 12a-c (1 mmol) in DMF (20 mL) was added sodium hydride (3 mmol) portion wise and the resulting reaction mixture was stirred at room temperature for 1 h. Next, a solution of alkyl halide (1.2 mmol) in DMF (2 mL) was added drop wise to reaction mixture and stirred for 12 h at room temperature. Upon completion of reaction, the contents were poured over crushed ice (100 gm) and extracted with DCM (3 × 30 mL), dried and removed the excess solvent under vaccuo. The residue so obtained was purified by column chromatography using ethyl acetate:hexane (1:1) as an eluent to afford N-alkylated β-carbolines 13a-c in 77-85% yields .
  • 75
  • [ 244-63-3 ]
  • [ 105-36-2 ]
  • 2-(9H-pyrido[3,4-b]indole-9-yl)ethyl acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
54% Stage #1: betacarboline With sodium hydride In N,N-dimethyl-formamide at 20℃; for 2h; Stage #2: ethyl bromoacetate In N,N-dimethyl-formamide at 20℃; for 5h;
54% Stage #1: betacarboline With sodium hydride In N,N-dimethyl-formamide at 20℃; for 2h; Stage #2: ethyl bromoacetate In dichloromethane at 20℃; for 5h; 1.1 Synthesis of Compound 2- (9H-pyrido [3,4-b] indole-9-yl) acetate (3) Will be purchased in the Palerick CAS No. 244-63-3;Product Compound No. 230515(0.50 g, 2.98 mmol)And NaH (0.24 g, 5.96 mmol) were placed in a round bottom flask,And then dissolved with 10 mL of DMF,After stirring at room temperature for 2 h,Compound 2 (0.49 mL, 4.46 mmol) was added dropwise to the above reaction solution at room temperature for 5 h,TLC detection of raw materials basic reaction completely.Water was added and extracted three times with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated. The crude product was purified by silica gel column chromatography(CH2C12: CH30H = 60: 1) to give compound 3 as pale yellow (0.40 g, yield 54%).
  • 76
  • [ 244-63-3 ]
  • [ 158690-56-3 ]
  • tert-butyl N-(2-(9H-pyrido[3,4-b]indole-9-yl)ethyl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
77% compound 1 (0.50 g, 2 . 98 mmol) and 60% NaH (0.24 g, 5 . 96 mmol) is placed in a round-bottom flask, then 10 mLDMF dissolved, 45 C stirring 2 h after, then the compound 2 (2.81 g, 8 . 94 mmol) is added in the reaction solution, stirring at the room temperature 16 h, TLC detection raw material the basic reaction is complete. Water, extracted with ethyl acetate 3 times, the organic layer by magnesium sulfate drying, the crude product is concentrated after silica gel column chromatography (CH2 Cl2 : CH3 OH=30:1) purification gets yellow solid compound 3 (0.74 g, yield 77%).
  • 77
  • [ 244-63-3 ]
  • [ 26690-80-2 ]
  • tert-butyl N-(2-(9H-pyrido[3,4-b]indole-9-yl)ethyl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
77% Stage #1: betacarboline With sodium hydride In N,N-dimethyl-formamide at 45℃; for 2h; Stage #2: 2-(N-tert-butoxycarbonylamino)ethanol In N,N-dimethyl-formamide at 20℃; for 16h; 1.4 Synthesis of tert-butyl (2- (9H-pyrido [3,4-b] indol-9-yl) ethyl) carbamate (8) Compound 1 (0.50 g, 2.98 mmol) and NaH (0.24 g, 5.96 mmol) were placed in a round bottom flask,And then dissolved with 10 mL of DMF,After stirring at 45 ° C for 2 h, compound 6 (2.81 g, 8.94 mmol) was added to the above reaction solution and stirred at room temperature for 16 h. TLC was used to determine the basic reaction of the starting material.The organic layer was dried over magnesium sulfate and concentrated. The crude product was purified by silica gel column chromatography (CH2Cl2: CH3OH = 30: 1) to give pale yellow solid compound 8 (0.74 g, yield 77%).
  • 78
  • [ 244-63-3 ]
  • [ 83817-43-0 ]
  • C25H16N4O [ No CAS ]
YieldReaction ConditionsOperation in experiment
46.2% With copper(l) iodide; potassium carbonate; <i>L</i>-proline In dimethyl sulfoxide at 90℃; for 48h; Inert atmosphere; F Synthesis of the compound of Chemical Formula (2): 2-CbOXD The compound 4 (0.5 g , 2.9 mmol), the compound 8 (1.0 g , 3.3 mmol), copper iodide (20.0 mg, 0.1 mmol), potassium carbonate (1.64g, 11.9 mmol), and L-proline (27.1 mg, 0.2 mmol) were placed in a double flask (5.00 mL), and dimethyl sulfoxide (0.65 mL) was injected under argon atmosphere. The mixture was heated to 90° C. and refluxed for 48 hours, followed by cooling to room temperature. The mixture was filtered through celite, purified by column chromatography, and eluted by the solution of dichloromethane and ethyl acetate (4:1 in v/v). The solvent was removed by using a rotary vacuum concentrator, and the compound of Chemical Formula (2) (2-CbOXD, 0.53 g) of yellow solid was obtained. The yield is 46.2%. Spectral data as follow: 1H NMR (400 MHz, d6-DMSO) : δ 8.48-8.45 (m,3H), 8.45 (d, J=2.0 Hz, 1H), 8.26 (dd, J=1.2, 1.2 Hz, 1H), 8.00-7.96 (m, 1H), 7.93-7.88 (m, 2H), 7.51-7.44 (m, 2H), 7.36-7.30 (m, 3H), 7.16-7.10 (m, 3H) ; 13C NMR (100 MHz, d6-DMSO) : δ 164.13, 162.19, 142.33, 140.26, 137.66, 134.45, 132.90, 132.51, 131.59, 131.37, 130.7, 129.56, 129.50, 128.80, 126.46, 122.98, 122.60, 121.56, 121.14, 115.31, 110.48. HRMS m/z [M+Na]+411.1216. ∘ Anal. Calcd for C44H29N5: C, 84.19; H, 4.66; N, 11.16; Found: C, 84.22; H, 4.70; N, 11.08. The reaction was shown as the following Equation (10).
  • 79
  • [ 244-63-3 ]
  • [ 590-17-0 ]
  • N2-(cyanomethyl)-9H-β-carbolinium bromide [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% In acetonitrile for 3h; Reflux; N2-(Cyanomethyl)-9H-β-carbolinium bromide (2). Bromoacetonitrile (0.84 ml, 12.0 mmol) was added to a solution of 9H-β-carboline (1) (1.00 g, 5.95 mmol) in MeCN (6 ml). The reaction mixture was refluxed for 3 h.The precipitate that formed was filtered off, washed threetimes with MeCN, and air-dried. Yield 1.54 g (90%), lightyellow crystals, mp 170-172°C (decomp.). IR spectrum,ν, cm-1: 3429 (NH), 2249 (CN), 1634, 1524, 1452. 1H NMR spectrum, δ, ppm (J, Hz): 6.13 (2H, s, CH2); 7.48-7.52 (1H, m, H-6); 7.84-7.87 (2H, m, H-5,7); 8.55 (1H, d,J = 8.0, H-8); 8.86 (1H, d, J = 6.5, H-4); 8.96 (1H,d, J = 6.5, H-3); 9.61 (1H, s, H-1); 13.05 (1H, s, NH).13C NMR spectrum, δ, ppm: 47.7; 113.8; 115.6; 118.8;119.6; 122.5; 124.5; 131.0; 133.3; 133.8 (2C); 135.3; 145.1.Mass spectrum, m/z: 208 [M-Br]+. Found, %: C 54.31;H 3.48; N 14.67. C13H10BrN3. Calculated, %: C 54.19;H 3.50; N 14.58.
  • 80
  • [ 244-63-3 ]
  • 4-([1,1'-biphenyl]-4-yl)-6-(3-bromophenyl)-2-phenylpyrimidine [ No CAS ]
  • C39H26N4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
17.6% With copper; potassium carbonate; sodium sulfate In nitrobenzene at 170 - 180℃; 6 Synthesis of compound 4-8 (WS15-30-147) 1To a 250 mL flask was added 3.81 g (22.7 mmol) of β-carboline, 7.00 g (15.1 mmol) of Intermediate 4, 192 mg (3.02 mmol) of Cu, 133 g (22.7 mmol) of K2CO3, , 22 g (22.7 mmol) and 75 mL of nitrobenzene and then stirred at 170-180 [deg.] C overnight. After the reaction was completed, the reaction mixture was cooled to room temperature and purified by silica gel column chromatography (EA: CHCl3). The solid was filtered using EA and MeOH to obtain 1.46 g (yield: 17.6%) of a yellow solid compound 4-8 (WS15- 30-147).
  • 81
  • [ 244-63-3 ]
  • 4-([1,1'-biphenyl]-4-yl)-6-(2-bromophenyl)-2-phenylpyrimidine [ No CAS ]
  • C39H26N4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
57% With copper; potassium carbonate; sodium sulfate In nitrobenzene at 170 - 180℃; 3 Synthesis of compound 4-4 (WS15-30-140) 12.0 g (11.9 mmol) of beta-carboline, 5.79 g (12.5 mmol) of Intermediate 6, 0.23 g (3.57 mmol) of Cu, 93.3 g (35.7 mmol) of K2CO3, Na2SO45. 07 g (35.7 mmol) and 60 mL of nitrobenzene and then stirred at 170-180 [deg.] C overnight. After the reaction was completed, the reaction mixture was cooled to room temperature and purified by silica gel column chromatography (EA: CHCl3). The solid was filtered using EA and MeOH to obtain 3.73 g (yield: 57%) of compound 4-4 (WS15-30-140) as a yellow solid.
  • 82
  • [ 244-63-3 ]
  • C27H18BrN3 [ No CAS ]
  • C38H25N5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
64% With copper(l) iodide; 1,10-Phenanthroline; caesium carbonate In 5,5-dimethyl-1,3-cyclohexadiene at 110 - 120℃; for 8h; 16 Synthesis of compound 4-19 (WS15-30-116) 25.0 g (10.7 mmol) of Intermediate (9), 1.97 g (11.7 mmol) of -carboline, 0.2 g (1.05mmol) of CuI and 1,10-phenanthroline -phenanthroline (0.38 g, 2.1 mmol), Cs2CO3 (0.01 g, 21.5 mmol) and xylene (300 mL), followed by stirring at 110-120 ° C for 8 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and purified by silica gel column chromatography to obtain 3.8 g (yield: 64%) of a solid compound 4-19 (WS15-30-116).
  • 83
  • [ 244-63-3 ]
  • C27H18BrN3 [ No CAS ]
  • C38H25N5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
38% With copper(l) iodide; 1,10-Phenanthroline; caesium carbonate In 5,5-dimethyl-1,3-cyclohexadiene at 110 - 120℃; for 14h; 11 Synthesis of compound 4-14 (WS15-30-122) 1A 500 mL flask was charged with 6.0 g (0.013 mol) of intermediate (12), 2.4 g (0.014 mol) of beta-carboline, 0.3 g (1.615 mmol) of CuI, 0.6 g (3.230 mmol) of 10- phenanthroline, 0.4 g (0.026 mol) of Cs2CO3 and 300 mL of xylene, followed by stirring at 110-120 DEG C for 14 hours. After the reaction was completed, the reaction mixture was cooled to room temperature and purified by silica gel column chromatography to obtain 2.7 g (yield: 38%) of a white solid compound 4-14 (WS15-30-122).
  • 84
  • [ 55934-00-4 ]
  • [ 62-53-3 ]
  • [ 244-63-3 ]
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