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Volumn , Issue 14, 2007, Pages 2237-2241

Synthesis of 6-substituted pyrido[2,3-b]indoles by electrophilic substitution

Author keywords

Acylations; Azacarbazole; Electrophilic aromatic substitutions; Halogenation; Heterocycles; Regioselectivity

Indexed keywords

INDOLE DERIVATIVE; PYRIDO[2,3 B]INDOLE; UNCLASSIFIED DRUG;

EID: 34548755519     PISSN: 09365214     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2007-985566     Document Type: Article
Times cited : (22)

References (46)
  • 33
    • 34548742868 scopus 로고    scopus 로고
    • Typical Procedure for Acylation: At r.t. and under an inert atmosphere, AlCl3 (714 mg, 5.36 mmol, 4.5 equiv) and acetyl chloride (178 μL, 2.38 mmol, 2 equiv) were added to a suspension of 4a (0.2 M, 200 mg, 1.19 mmol) in anhyd CH2Cl2. The mixture was stirred at reflux until completion of the reaction (monitored by TLC, In the case of methyl oxalyl chloride and oxalyl chloride, the chloride was added as a 50% solution in CH2Cl2 and the reaction was stirred at r.t. The resulting mixture was then cautiously quenched at 0°C with H 2O. The mixture was extracted with a mixture of EtOAc-DMF (99:1, The resulting organic layer was washed with a sat. aq NaHCO3 solution and brine, dried over MgSO4, filtered, and solvents were removed under reduced pressure. Trituration of the crude residue from MeOH followed by filtration afforded 6-acetylpyrido[2,3-b]indole 5a (168 mg) as
    • 2O: C, 74.27; H, 4.79; N, 13.32. Found: C, 74.35; H, 4.81; N, 13.26.
  • 34
    • 34548744591 scopus 로고    scopus 로고
    • Analytical Data of Compound 6: The compound 6 was obtained by flash chromatography [gradient: EtOAc-PE (1:1) → EtOAc, yield: 90, white solid; mp 207°C (MeOH, IR (KBr, 3049, 2850, 1734, 1622, 1599, 1496, 1473, 1408, 1234, 1201,752 cm-1. 1H NMR (300 MHz, DMSO-d6, δ, 12.5 (brs, 1 H, NH, 8.86 (d, J, 1.5 Hz, 1 H, H-5, 8.74 (dd, J, 1.6, 7.8 Hz, 1 H, H-4, 8.52 (dd, J, 1.6, 4.9 Hz, 1 H, H-2, 8.05 (dd, J, 1.5, 8.6 Hz, 1 H, H-7, 7.66 (d, J, 8.6 Hz, 1 H, H-8, 7.33 (dd, J, 4.9, 7.8 Hz, 1 H, H-3, 4.00 (s, 3 H, Me, 13C NMR (75 MHz, DMSO-d6, δ, 186.2 (CO, 165.3 (CO, 152.7 (C, 147.9 (CH, 143.2 (C, 129.7 (CH, 127.9 (CH, 125.1 (CH, 123.4 (C, 120.7 (C, 116.4 (CH, 115.3 (C, 112.0 (C, 52.9 (Me, MS ESI, m/z, 255 [M, H, Anal. Calcd for C14H10N2O3: C, 66.14; H, 3
    • 3: C, 66.14; H, 3.96; N, 11.02. Found: C, 66.22; H, 4.03; N, 10.92.
  • 35
    • 34548764923 scopus 로고    scopus 로고
    • Analytical Data of Compound 7: The compound 7 was obtained by trituration from MeOH; yield: 71, white solid; mp >295°C (MeOH, IR (KBr, 3219, 1682, 1597, 1493, 1476, 1405, 909, 746 cm-1. 1H NMR (300 MHz, DMSO-d6, δ, 12.73 (br s, 1 H, OH, 12.18 (br s, 1 H, NH, 8.83 (br s, 1 H, H-5, 8.66(dd, J, 1.6, 7.6 Hz, 1 H, H-4, 8.47 (dd, J, 1.6, 4.9 Hz, 1 H, H-2, 8.06 (dd, J, 1.7, 8.6 Hz, 1 H, H-7, 7.55 (d, J, 8.6 Hz, 1 H, H-8, 7.27 (dd, J, 4.9, 7.6 Hz, 1 H, H-3, 13C NMR (75 MHz, DMSO-d6, δ, 167.9 (CO, 152.5 (C, 146.8 (CH, 141.7 (C, 129.2 (CH, 127.9 (CH, 123.5 (CH, 121.9 (C, 120.2 (C, 115.8 (CH, 115.4 (C, 111.0 (CH, MS (EI, m/z, 212 [M+·, HRMS EI, m/z calcd for C12H8N2O2: 212.0586; found: 212.0584
    • 2: 212.0586; found: 212.0584.
  • 36
    • 34548748095 scopus 로고    scopus 로고
    • Analytical Data for Compound 8: The compound 8 was obtained by flash chromatography [gradient: EtOAc-PE (1:1) → EtOAc, yield: 78, white solid; mp 212°C (MeOH, IR (KBr, 3040, 1647, 1603, 1565, 1494, 1466, 1254, 769, 702 cm-1. 1H NMR (300 MHz, DMSO-d 6, δ, 12.29 (br s, 1 H, NH, 8.65-8.67 (m, 2 H, H-4, H-5, 8.48 (dd, J, 1.5, 4.9 Hz, 1 H, H-2, 7.90 (dd, J, 1.5, 8.0 Hz, 1 H, H-7, 7.76-7.79 (m, 2 H, Har, 7.56-7.68 (m, 4 H, H-8, H ar, 7.26 (dd, J, 4.9, 8.0 Hz, 1 H, H-3, 13C NMR (75 MHz, DMSO-d6, δ, 195.5 (CO, 152.6(C, 147.0 (CH, 141.7 (C, 138.3 (C, 132.0 (CH, 129.5 (2 x CH, 129.4 (CH, 128.7 (CH, 128.6 (C, 128.5 (2 x CH, 124.3 (CH, 120.4 (C, 115.9 (CH, 115.5 (C, 111.1 (CH, MS ESI, m/z, 273 [M, H, Anal. Calcd for C 18H12N2O: C, 79.40; H, 4.44; N, 10.29. Found
    • 2O: C, 79.40; H, 4.44; N, 10.29. Found: C, 79.48; H, 4.44; N, 10.29.
  • 40
    • 34548794792 scopus 로고    scopus 로고
    • Typical Procedure and Analytical Data for Compound 9: At -78°C and under an inert atmosphere, AlCl3 (714 mg, 5.36 mmol, 4.5 equiv) was added portionwise to a suspension of 4a (0.02 M, 200 mg, 1.19 mmol) in anhyd CH2Cl2. After stirring for 5 min, α,α-dichloromethyl methyl ether (318 μL, 3.57 mmol, 3 equiv) was added dropwise to the mixture. The reaction mixture was stirred at -78°C and then allowed to warm to r.t. for 12 h. The resulting mixture was then cautiously quenched at 0°C with H2O and extracted with a mixture of EtOAc-DMF (99:1, The combined organic layers were washed with a sat. aq NaHCO3 solution, dried with MgSO4, filtered and evaporated under reduced pressure. The crude residue was purified by flash chromatography (EtOAc-PE, 1:1) to afford 9 (100 mg, 46, as a white solid; mp 262°C (MeOH, IR KBr, 3043, 3014, 2824, 1690, 1604, 1569, 1470, 1410, 761 cm
    • 2O: C, 73.46; H, 4.11; N, 14.28. Found: C, 73.15; H, 4.39; N, 14.28.
  • 41
    • 34548768212 scopus 로고    scopus 로고
    • Typical Procedure and Analytical Data for Compound 10: At r.t. and under an inert atmosphere, a solution of bromine (1.2 equiv, 0.7 M) in anhyd CH2Cl2 was added to a suspension of 4a (0.45 M, 200 mg, 1.19 mmol) in anhyd CH2Cl2. The mixture was stirred for 1 h at r.t. Excess bromine was destroyed by addition of a sat. aq Na 2S2O3 solution. The resulting mixture was extracted with EtOAc-DMF (99:1, The combined organic phases were washed with brine, dried over MgSO4, filtered and evaporated under reduced pressure. Trituration of the crude residue from MeOH followed by filtration afforded 10 (241 mg, The filtrate was evaporated and purified by flash chromatography [gradient: EtOAc-PE (1:1) → EtOAc] to give additional 10 (27 mg, yield: 91, mp 250°C (MeOH, lit.15a mp 266-270°C, IR KBr, 3052, 1604, 1586, 1493, 1448, 768, 610 cm -1
    • 2: 245.9793; found: 245.9797
  • 44
    • 34548750353 scopus 로고    scopus 로고
    • 2 salt suggests a possible involvement of an N-nitro intermediate. Further studies are underway to clarify the origin of the selectivity.
    • 2 salt suggests a possible involvement of an N-nitro intermediate. Further studies are underway to clarify the origin of the selectivity.
  • 45
    • 34548794793 scopus 로고    scopus 로고
    • Analytical Data for Compound 13: mp >295°C (MeOH, lit.15a mp >320°C, IR (KBr, 3066, 1612, 1587, 1573, 1498, 1456, 1327, 749 cm-1. 1H NMR (300 MHz, DMSO-d 6, δ, 12.58 (brs, 1 H, NH, 9.25 (d, J =2.2 Hz, 1 H, H-5, 8.80 (dd, J, 1.7, 7.8 Hz, 1 H, H-4, 8.54 (dd, J, 1.7, 4.8 Hz, 1 H, H-2, 8.35 (dd, J =2.2, 9.0 Hz, 1 H, H-7, 7.65 (d, J, 9.0 Hz, 1 H, H-8, 7.35 (dd, J, 4.8, 7.8 Hz, 1 H, H-3, 13C NMR (75 MHz, DMSO-d6, δ, 153.0 (C, 147.9 (CH, 142.6 (C, 140.5 (C, 130.2 (CH, 122.2 (CH, 120.3 (C, 118.4 (CH, 116.6 (CH, 115.5 (C, 111.6 (CH, MS (ESI, m/z, 214 [M, H, HRMS ESI, m/z [M, H, calcd for C11H7N 3O2: 214.0617; found: 214.1017
    • 2: 214.0617; found: 214.1017.
  • 46
    • 34548713457 scopus 로고    scopus 로고
    • Analytical Data for Compound 14: mp 253°C (MeOH, IR (KBr, 3046, 1600, 1573, 1525, 1474, 1362, 732 cm-1. 1H NMR (300 MHz, DMSO-d6, δ, 12.15 (br s, 1 H, NH, 8.63 (dd, J, 1.5, 7.7 Hz, 1 H, H-4, 8.62 (d, J, 7.7 Hz, 1 H, H-7, 8.58 (dd, J, 1.5, 4.8 Hz, 1 H, H-2, 8.35 (d, J, 8.2 Hz, 1 H, H-5, 7.43 (dd, J, 7.7, 8.2 Hz, 1 H, H-6, 7.36 (dd, J, 4.8, 7.7 Hz, 1 H, H-3, 13C NMR (75 MHz, DMSO-d6, δ, 152.4 (C, 147.6 (CH, 132.1 (C, 131.9 (C, 128.9 (CH, 128.1 (CH, 124.5 (C, 122.1 (CH, 118.9 (CH, 116.5 (CH, 114.0 (CH, MS (EI, m/z, 213 [M+·, HRMS EI, m/z calcd for C11H 7N3O2: 213.0538; found: 213.0535
    • 2: 213.0538; found: 213.0535.


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.