(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 47540

反応式

HRID 47540 の反応式
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

参加物

5

反応物 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

生成物 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]indole収率 45%

試薬・触媒・溶媒 2

HCID 80711,2-Dimethoxyethane溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
85 °C

実験手順

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)+.

後処理

  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)

出典と根拠

ORDレコード
ord-fbce81c6e60c47c0bd9a80d2a7b4454b
出典データセット
uspto-grants-2004_03
特許番号
US06699852B2

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