gamma-carboline

General procedure: A mixture of 2'-methoxy- 2-nitrobiphenyl (Compound 6a-l, 520 mg, 2.26 mmol) and triphenylphosphine (1.48 g, 5.67 mmol) in chlorobenzene (6 mL) was heated at 200 C for 2 h under microwave irradiation. The mixture was evaporated and the residue purified by column chromatography eluting with hexane:ethyl acetate (20: 1) to give the title compound (335 mg, 1.70 mmol, 75%) as a white powder. LCMS: 88%, RT 1.678, ESMS m/z 198 (M+H)+.A mixture of 3-bromo-N-phenylpyridin-4-amine (0.87 g, 3.49 mmol), palladium acetate (78.4 mg, 0.35 mmol), DUB (1.1 g, 6.99 mmol) and DCHPB (0.24 g, 0.70 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 5H-pyrido[4, 3-b]indole (0.30 g, 51.1% yield) as a yellow solid. LC/MS (ESI, m/z): [M+1]+=169.3.To a sealed tube equipped with a magnetic stir bar was added 4- (2'-bromoanilino) pyridine (2.48 g, 9.96 mmol) Pd (OAc) 2 (112 mg, 4.98 mmol) and Na2CO3 (1.48 g, 13.9 mmol). The mixture was purged with nitrogen and DMF (20 mL) was added.The resulting mixture was stirred at 160 for 20 hours.The reaction mixture was cooled to ambient temperature.The mixture was filtered through Celite pad and washed with CH2Cl2.The filtrate was concentrated in vacuo, the residue was diluted with H2O (12 mL), worked up with EtOAc (20 mL x 6)Dried over MgSO4, and concentrated in vacuo.The residue was subjected to flash column chromatography (5% MeOH in CH2Cl2 followed by 15% MeOH in CH2Cl2) to give 5H-pyrido [4, 3-b] indole (1.26 g, 75% yield)N-(2-Bromophenyl)pyridin-4-amine (25 g, 100 mmol), Pd(OAc) 2 (1.12 g, 5 mmol) and sodium carbonate (14.8 g, 140 mmol), Dissolve in DMF (200ml), heat to 75 C under N2 atmosphere, react for 20h, after cooling to room temperature, add the mixture to dilute the mixture with ethyl acetate.Then washed repeatedly with water, the combined organic phases were vigorously stirred with 2M hydrochloric acid, the organic phase was extracted, then the aqueous mixture was mixed and neutralized with NaOH until neutral.At this time, a large amount of gray-white flocculent precipitate was formed, filtered, and dried to obtain an intermediate (5), an off-white product, 17 g, yield 70%.Next, the compound 5 (7.5 g , 30.2 mmol), palladium(II) acetate (336.0 mg, 1.5 mmol), sodium carbonate (4.44 g, 42.0 mmol), and dimethylformamide (60.00 mL) were mixed and heated to 165 C. and refluxed for 24 hours, followed by cooling to room temperature. The mixture was filtered through celite and washed with ethyl acetate. Most of the ethyl acetate was removed by using a rotary vacuum concentrator. Sodium hydroxide was added to the solution directly until the solution was neutral. A black suspension was formed and the solution was filtered by suction to remove the suspension and to collect the filtrate. After continuously adding with sodium hydroxide, a large amount of white precipitation was formed. The mixture was filtered by suction and the white precipitation was collected. After washed by ether, the compound 6 (gamma-carboline) was obtained, and the yield is 50.89%. Spectral data as follow: 1H NMR (400 MHz, d6-DMSO) : delta 11.71 (s, 1H), 9.33 (s, 1H), 8.42 (d, J=5.6 Hz, 1H), 8.23 (d, J=8.0 Hz, 1H), 7.57-7.55 (m, 1H), 7.49-7.45 (m, 2H), 7.28-7.24 (m, 1H) ; 13C NMR (100 MHz, d6-DMSO) : delta 203.10, 144.00, 143.00, 142.24, 139.01, 126.07, 120.20, 120.09, 119.45, 118.89, 110.95, 105.84Compound 5 (7.5 g, 30.2 mmol), palladium(II) acetate (336.0 mg, 1.5 mmol), sodium carbonate (4.44 g, 42.0 mmol) were added in 60.0 mL of dimethylformamide and followed by refluxed at 165 C. for 24 hours. Then the temperature was returned to room temperature. The mixture was filtered through celite and washed with ethyl acetate. Then, the most of ethyl acetate was removed in a rotary evaporator. NaOH was added in the solution until a neutral pH to obtain a black suspension. The filtrate was collected by suction filtration and followed by added NaOH. Then a large amount of white solid was precipitated. The solid was collected by suction filtration and followed by washed with ether to obtain compound 6 (5H-pyrido[4, 3-b]indole, i.e. gamma-carboline, yield: 50.89%). Spectral data as follow: 1H NMR (400 MHz, d6-DMSO): delta 11.71 (s, 1H), 9.33 (s, 1H), 8.42 (d, J=5.6 Hz, 1H), 8.23 (d, J=8.0 Hz, 1H), 7.57-7.55 (m, 1H), 7.49-7.45 (m, 2H), 7.28-7.24 (in, 1H); 13C NMR (100 MHz, d6-DMSO): delta 203.10, 144.00, 143.00, 142.24, 139.01, 126.07, 120.20, 120.09, 119.45, 118.89, 110.95, 105.84.

Molecular Weight:168.19
XLogP3:2.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Exact Mass:168.068748264
Monoisotopic Mass:168.068748264
Topological Polar Surface Area:28.7
Heavy Atom Count:13
Complexity:193
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes