(4-Methoxy-2-methylphenyl)boronic acid → (7bR,11aS)-6-(4-methoxy-2-methylphenyl)-1,2,7b,8,9,10,11,11a-octahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indole

HRID 23260

Reaktionsgleichung

Reaktionsgleichung von HRID 23260
Br[C:2]1[CH:3]=[C:4]2[C:8]3=[C:9]([CH2:11][S:12][CH2:13][CH2:14][N:7]3[C@H:6]3[CH2:15][CH2:16][N:17](C(OC(C)(C)C)=O)[CH2:18][C@@H:5]23)[CH:10]=1.[CH3:26][C:27]1[CH:32]=[C:31]([O:33][CH3:34])[CH:30]=[CH:29][C:28]=1B(O)O>COCCOC.C(OCC)(=O)C>[CH3:34][O:33][C:31]1[CH:30]=[CH:29][C:28]([C:2]2[CH:3]=[C:4]3[C:8]4=[C:9]([CH2:11][S:12][CH2:13][CH2:14][N:7]4[C@H:6]4[CH2:15][CH2:16][NH:17][CH2:18][C@@H:5]34)[CH:10]=2)=[C:27]([CH3:26])[CH:32]=1

Komponenten

5

Edukt 2

HCID 2773486(4-Methoxy-2-methylphenyl)boronic acidHCID 86586435tert-butyl (7bR,11aS)-6-bromo-1,2,7b,10,11,11a-hexahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indole-9(8H)-carboxylate

Produkt 1

HCID 59984897(7bR,11aS)-6-(4-methoxy-2-methylphenyl)-1,2,7b,8,9,10,11,11a-octahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indoleAusbeute 45 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 80711,2-DimethoxyethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

To a solution of tert-butyl (7bR,11aS)-6-bromo-1,2,7b,10,11,11a-hexahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indole-9(8H)-carboxylate from EXAMPLE 7, Part A (80 mg, 0.18 mmol) in 25 mL of DME (10 mL) was added 2-methyl 4 methoxyphenyl boronic acid (45 mg, 0.27 mmol) and TEA (0.26 mL, 1.8 mmol). The mixture was degassed with a stream of nitrogen for 20 min and then there was added Pd(dppf)2 (15 mg, 0.1 mmol) and the mixture was stirred at 85° C. for 16 h. The reaction was allowed to cool to ambient temperature and was diluted with ethyl acetate, washed with sat'd aqueous sodium bicarbonate and brine, dried (MgSO4), filtered through Celite and concentrated in vacuo. The residue was purified by flash chromatography (elution with hexanes/ethyl acetate) to afford (35 mg, 45% yield) of the title compound. 1H NMR (CDCl3, 300 MHz): δ 7.13 (d, 1H, J=8.1 Hz), 6.97 (s, 1H), 6.75 (m, 3H), 3.83 (s, 3H), 3.79 (m, 1H), 3.65 (m, 2H), 3.52 (m, 3H), 3.21 (m, 2H), 3.01 (m, 2H), 2.24 (s, 3H), 1.97 (m, 2H), 1.60)m, 2H), 1.21 (s, 9H). LRMS (ES+): 467 (M+H)+.

Aufarbeitung

  1. customThe mixture was degassed with a stream of nitrogen for 20 min
  2. temperatureto cool to ambient temperature
  3. washwashed with sat'd aqueous sodium bicarbonate and brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered through Celite
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography (elution with hexanes/ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-378e649375ff4ac981ad7db88aa33439
Quelldatensatz
uspto-grants-2005_02
Patentnummer
US06849619B2

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