Oncrasin 1 → [1-(4-Chloro-benzyl)-1H-indol-3-yl]-[4-pyridin-2-yl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-methanol

HRID 352147Notes

Reaction equation

HRID 352147 reaction equation
C([N-]C(C)C)(C)C.[Li+].C(C1C=CC=CC=1)C.C1COCC1.[CH3:22][Si:23]([CH3:40])([CH3:39])[CH2:24][CH2:25][O:26][CH2:27][N:28]1[CH:32]=[C:31]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=2)[N:30]=[CH:29]1.[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:29]3[N:28]([CH2:27][O:26][CH2:25][CH2:24][Si:23]([CH3:40])([CH3:39])[CH3:22])[CH:32]=[C:31]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=4)[N:30]=3)[OH:57])=[CH:48]2)=[CH:58][CH:59]=1

Participants

6

Reactant 4

HCID 872445Oncrasin 1HCID 2724682Lithium diisopropylamideHCID 12146867HCID 12146867, compoundHCID 68569164HCID 68569164, compound

Product 1

HCID 12146868[1-(4-Chloro-benzyl)-1H-indol-3-yl]-[4-pyridin-2-yl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-methanolYield 87%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Lithium diisopropylamide (2 M solution in petane/ethylbenzene/THF, 57 uL, 0.12 mmol) was added to a stirred solution of 2-[1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-4-yl]-pyridine (10.5 mg, 0.038 mmol) in dry THF (3 mL) at −78° C. under N2. After 1 hour at this temperature, a solution of N-4-chlorobenzylindole-3-carboxaldehyde (31 mg, 0.12 mmol) in dry THF (1 mL) was then added through a cannula. The resultant clear solution was stirred at −78° C. for 2 hours. The temperature was then allowed to rise to room temperature and the reaction was quenched by the addition of saturated aqueous NH4Cl (5 mL), extracted with dichloromethane (3×10 mL). The organic layer was separated, dried (Na2SO4), and concentrated under reduced pressure. Flash silica gel chromatography (4:1 hexane/ethyl acetate then 2:1 ethyl acetate/hexane then 4:1 ethyl acetate/MeOH) provided the product [1-(4-Chloro-benzyl)-1H-indol-3-yl]-[4-pyridin-2-yl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-methanol as a light yellow syrup (18 mg, 87%). 1H NMR δ−0.05 (s, 9H), 0.81 (t, 2H, J=7), 3.38 (t, 2H, J=7), 5.05-5.35 (m, 5H), 6.30 (s, 1H), 6.95-7.30 (m, 9H), 7.45 (d, 1H, J=6), 7.65 (s, 1H), 7.71 (t, 1H, J=6), 8.05 (d, 1H, J=6), 8.60 (d, 1H, J=4)ppm; ESMS calcd for (C30H33ClN4O2Si): 544.2; found: 545.2 (M+H)+.

Workup

  1. customto rise to room temperature
  2. customthe reaction was quenched by the addition of saturated aqueous NH4Cl (5 mL)
  3. extractionextracted with dichloromethane (3×10 mL)
  4. customThe organic layer was separated
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-0540411073074bfeb4f8009130ad9921
Source dataset
uspto-grants-2004_06
Patent number
US06743919B2

Reaction notes

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