Sodium Carbonate → 7-(quinolin-3-yl)-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole

HRID 37814Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 37814
Br[C:2]1[C:10]2[NH:9][C:8]3[CH:11]4[CH2:17][CH2:16][N:14]([CH2:15][C:7]=3[C:6]=2[CH:5]=[CH:4][CH:3]=1)[CH2:13][CH2:12]4.[N:18]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:21]=[C:20](B(O)O)[CH:19]=1.C(=O)([O-])[O-].[Na+].[Na+]>CC(O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[N:18]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:21]=[C:20]([C:2]2[C:10]3[NH:9][C:8]4[CH:11]5[CH2:17][CH2:16][N:14]([CH2:15][C:7]=4[C:6]=3[CH:5]=[CH:4][CH:3]=2)[CH2:13][CH2:12]5)[CH:19]=1

Komponenten

6

Edukt 3

HCID 10340Sodium CarbonateHCID 2734663Quinoline-3-boronic acidHCID 672401637-bromo-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole

Produkt 1

HCID 532517347-(quinolin-3-yl)-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418476HCID 178418476, VerbindungKatalysatorHCID 3776IsopropanolLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A suspension of the product of Example 1B (150 mg, 0.52 mmol), 3-quinolineboronic acid (102 mg, 0.59 mmol; Aldrich), dichlorobis(triphenylphosphine)palladium (II) (18 mg, 0.026 mmol; Aldrich) and 1.0 M sodium carbonate (1.3 mL) in 2-propanol (3.8 mL) was purged with nitrogen and then stirred at 80° C. for 1 hour in a sealed tube. The reaction mixture was cooled and partitioned between CHCl3 (2×30 mL) and 1.0 M sodium carbonate (50 mL). The combined organic extracts were dried (sodium sulfate) and concentrated under vacuum. The resulting residue was purified by reverse-phase HPLC [Waters XBridge™RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 40-100% gradient of methanol in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)] to afford the title compound: 1H NMR (400 MHz, methanol-d4) δ ppm 1.98-2.16 (m, 4 H), 3.02-3.14 (m, 3 H), 3.25 (ddd, J=14.1, 8.8, 5.5 Hz, 2 H), 4.28 (s, 2 H), 7.12-7.22 (m, 2 H), 7.39 (dd, J=7.3, 1.5 Hz, 1 H), 7.66 (ddd, J=8.1, 7.0, 1.1 Hz, 1 H), 7.79 (ddd, J=8.5, 6.9, 1.4 Hz, 1 H), 8.03 (dd, J=8.2, 0.9 Hz, 1 H), 8.09 (d, J=8.5 Hz, 1 H), 8.57 (d, J=2.1 Hz, 1 H), 9.09 (d, J=2.1 Hz, 1 H); MS (ESI+) m/z 340 (M+H)+.

Aufarbeitung

  1. customwas purged with nitrogen
  2. temperatureThe reaction mixture was cooled
  3. custompartitioned between CHCl3 (2×30 mL) and 1.0 M sodium carbonate (50 mL)
  4. dry with materialThe combined organic extracts were dried (sodium sulfate)
  5. concentrationconcentrated under vacuum
  6. customThe resulting residue was purified by reverse-phase HPLC [Waters XBridge™RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 40-100% gradient of methanol in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)]

Quellen und Nachweise

ORD-Eintrag
ord-ecbc23aa801f4089aa9d57bfbfbf440b
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08524703B2

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