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Hexane → [1-(4-chloro-benzyl)-1H-indol-3-yl]-[4-pyridin-2-yl-5-(toluene-4-sulfonyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-methanol

HRID 1793612
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HRID 1793612 반응식
[C:1]1([CH3:29])[CH:6]=[CH:5][C:4]([S:7]([C:10]2[N:14]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[CH:13]=[N:12][C:11]=2[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=2)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[Li]CCCC.CCCCCC.[Cl:41][C:42]1[CH:59]=[CH:58][C:45]([CH2:46][N:47]2[C:55]3[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=3)[C:49]([CH:56]=[O:57])=[CH:48]2)=[CH:44][CH:43]=1>C1COCC1>[Cl:41][C:42]1[CH:43]=[CH:44][C:45]([CH2:46][N:47]2[C:55]3[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=3)[C:49]([CH:56]([C:13]3[N:14]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[C:10]([S:7]([C:4]4[CH:5]=[CH:6][C:1]([CH3:29])=[CH:2][CH:3]=4)(=[O:9])=[O:8])=[C:11]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=4)[N:12]=3)[OH:57])=[CH:48]2)=[CH:58][CH:59]=1
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참가 물질

6

반응물 4

HCID 8058HexaneHCID 872445Oncrasin 1HCID 121468712-[5-(Toluene-4-sulfonyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-4-yl]-pyridineHCID 178418339Butyllithium

생성물 1

HCID 12146872[1-(4-chloro-benzyl)-1H-indol-3-yl]-[4-pyridin-2-yl-5-(toluene-4-sulfonyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-methanol수율 30%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

To a stirred solution of 2-[5-(toluene-4-sulfonyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-4-yl]-pyridine (0.15 g, 0.35 mmol) in dry THF (10 mL) was added 2.5 M n-BuLi solution in hexane (0.21 mL, 0.525 mmol) under N2 at −78° C. After 20 minutes at this temperature, a solution of N-4-chlorobenzylindole-3-carboxaldehyde (0.1 g, 0.37 mmol) in dry THF (3 mL) was then added through a cannula. Stirring was continued at this temperature for 1 hour. The reaction was then quenched with H2O (10 mL) at 0° C. The aqueous solution was extracted with dichloromethane (3×15 mL). Combined dichloromethane solution was washed with brine and dried over Na2SO4. After removal of the solvent under reduced pressure, the crude material was separated by silica gel chromatography (2:1 hexane/ethyl acetate to 2:1 ethyl acetate/hexane) to afford the desired intermediate [1-(4-chloro-benzyl)-1H-indol-3-yl]-[4-pyridin-2-yl-5-(toluene-4-sulfonyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-methanol as an oil (65 mg, 30%). 1H NMR (CDCl3) δ −0.05 (s, 9H), 0.70 (t, 2h, J=6), 2.55 (s, 3H), 3.2–3.35 (m, 2H), 4.02 (d, 1H, J=7), 5.2–5.4 (m, 2H), 5.41 (s,2H), 6.4 (d, 1H), 7.0–8.0 (m, 16 H), 8.8 (d, 1H J=5). ESMS calcd for (C37H39ClN4O4SSi): 698.6; found: 699.6 (M+H)+.

후처리

  1. waitwas continued at this temperature for 1 hour
  2. customThe reaction was then quenched with H2O (10 mL) at 0° C
  3. extractionThe aqueous solution was extracted with dichloromethane (3×15 mL)
  4. washCombined dichloromethane solution was washed with brine
  5. dry with materialdried over Na2SO4
  6. customAfter removal of the solvent under reduced pressure
  7. customthe crude material was separated by silica gel chromatography (2:1 hexane/ethyl acetate to 2:1 ethyl acetate/hexane)

출처 및 근거

ORD 기록
ord-bc17dbd7d8ca41a3b3c7c7c6e9e646f3
출처 데이터셋
uspto-grants-2006_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07081466B2

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