3-Iodo-1-[tris(1-methylethyl)silyl]-1H-pyrrolo[2,3-b]pyridine → 5-Chloro-2-{5-fluoro-4-[hydroxy-(1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methyl]-2-methoxy-phenoxymethyl}-benzimidazole-1-carboxylic acid tert-butyl ester

HRID 253466Notes

Reaction equation

HRID 253466 reaction equation
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][CH:9]=2)[N:4]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[CH:3]=1.C([Mg][Cl:25])(C)C.[C:26]([O:30][C:31]([N:33]1[C:37]2[CH:38]=[C:39](Cl)[CH:40]=[CH:41][C:36]=2[N:35]=[C:34]1[CH2:43][O:44][C:45]1[CH:50]=[C:49]([F:51])[C:48]([CH:52]=[O:53])=[CH:47][C:46]=1[O:54][CH3:55])=[O:32])([CH3:29])([CH3:28])[CH3:27]>O1CCCC1>[C:26]([O:30][C:31]([N:33]1[C:37]2[CH:38]=[CH:39][C:40]([Cl:25])=[CH:41][C:36]=2[N:35]=[C:34]1[CH2:43][O:44][C:45]1[CH:50]=[C:49]([F:51])[C:48]([CH:52]([OH:53])[C:2]2[C:10]3[C:5](=[N:6][CH:7]=[CH:8][CH:9]=3)[N:4]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[CH:3]=2)=[CH:47][C:46]=1[O:54][CH3:55])=[O:32])([CH3:29])([CH3:28])[CH3:27]

Participants

5

Reactant 3

HCID 242292273-Iodo-1-[tris(1-methylethyl)silyl]-1H-pyrrolo[2,3-b]pyridineHCID 86623133HCID 86623133, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 668894835-Chloro-2-{5-fluoro-4-[hydroxy-(1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methyl]-2-methoxy-phenoxymethyl}-benzimidazole-1-carboxylic acid tert-butyl esterYield 44%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-5 °C

Procedure

3-Iodo-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine (68, 0.200 g, 0.5 mmol, prepared as described in Example 22) was dissolved in tetrahydrofuran (3 mL, 40 mmol). After the reaction reached the temperature of −20° C., a solution of 2M of isopropylmagnesium chloride in tetrahydrofuran (300 μL) was added dropwise. The resulted mixture was stirred to −5° C. After cooling the reaction to −20° C., a solution of 6-chloro-2-(5-fluoro-4-formyl-2-methoxy-phenoxymethyl)-benzoimidazole-1-carboxylic acid tert-butyl ester (152, 0.2 g, 0.46 mmol) in tetrahydrofuran (4 mL) was added at once to the mixture. The reaction warmed to −5° C. and was then evaporated to dryness under reduced pressure. Ethyl acetate was added. The organic portion was washed with saturated sodium bicarbonate solution, brine, dried over anhydrous sodium sulfate and concentrated. Purification with silica gel flash chromatography eluting with a gradient of ethyl acetate (5 to 80%) in hexanes gave the desired compound (153, 0.142 g, 44%). MS (ESI) [M+H+]+=709.4.

Workup

  1. customthe temperature of −20° C.
  2. temperatureAfter cooling
  3. customthe reaction to −20° C.
  4. temperatureThe reaction warmed to −5° C.
  5. customwas then evaporated to dryness under reduced pressure
  6. additionEthyl acetate was added
  7. washThe organic portion was washed with saturated sodium bicarbonate solution, brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated
  10. customPurification with silica gel flash chromatography
  11. washeluting with a gradient of ethyl acetate (5 to 80%) in hexanes

Sources & evidence

ORD record
ord-1f47218bc9a54757b6ec84e8271b7474
Source dataset
uspto-grants-2011_01
Patent number
US07872018B2

Reaction notes

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