(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

반응식

HRID 23260 반응식
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

참가 물질

5

반응물 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

생성물 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]indole수율 45%

시약·촉매·용매 2

HCID 80711,2-Dimethoxyethane용매HCID 8857Ethyl Acetate용매

반응 조건

온도
85 °C

실험 절차

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)+.

후처리

  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)

출처 및 근거

ORD 기록
ord-378e649375ff4ac981ad7db88aa33439
출처 데이터셋
uspto-grants-2005_02
특허 번호
US06849619B2

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