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 1793612Notes

Reaction equation

HRID 1793612 reaction equation
[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

Participants

6

Reactant 4

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

Product 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]-methanolYield 30%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

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)+.

Workup

  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)

Sources & evidence

ORD record
ord-bc17dbd7d8ca41a3b3c7c7c6e9e646f3
Source dataset
uspto-grants-2006_07
Patent number
US07081466B2

Reaction notes

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