Acetonitrile → 2-[4-(5-Chloro-1H-pyrrolo[2, 3-b]pyridin-3-ylmethyl)-5-fluoro-2-methoxy-phenoxymethyl]-1-methyl-1H-benzimidazole

HRID 253463Notes

Reaction equation

HRID 253463 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([CH:11]([C:13]3[CH:18]=[C:17]([O:19][CH3:20])[C:16]([O:21][CH2:22][C:23]4[N:27]([CH3:28])[C:26]5[CH:29]=[CH:30][CH:31]=[CH:32][C:25]=5[N:24]=4)=[CH:15][C:14]=3[F:33])O)=[CH:9][N:8]([Si](C(C)C)(C(C)C)C(C)C)[C:5]2=[N:6][CH:7]=1.C(#N)C.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([CH2:11][C:13]3[C:14]([F:33])=[CH:15][C:16]([O:21][CH2:22][C:23]4[N:27]([CH3:28])[C:26]5[CH:29]=[CH:30][CH:31]=[CH:32][C:25]=5[N:24]=4)=[C:17]([O:19][CH3:20])[CH:18]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

Participants

5

Reactant 4

HCID 6342AcetonitrileHCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 66888056(5-Chloro-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-[2-fluoro-5-methoxy-4-(1-methyl-1H-benzoimidazol-2-ylmethoxy)-phenyl]-methanol

Product 1

HCID 249562922-[4-(5-Chloro-1H-pyrrolo[2, 3-b]pyridin-3-ylmethyl)-5-fluoro-2-methoxy-phenoxymethyl]-1-methyl-1H-benzimidazoleYield 34%

Conditions

Temperature
70 °C

Procedure

(5-Chloro-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-[2-fluoro-5-methoxy-4-(1-methyl-1H-benzimidazol-2-ylmethoxy)-phenyl]-methanol (145) (0.140 g, 0.225 mmol) was suspended in acetonitrile (5 ml, 100 mmol). Triethylsilane (1.0 mL, 6.3 mmol) was added followed by trifluoroacetic acid (0.500 mL, 6.4 mmol). After the reaction was stirred at 60-80° C. for 1.5 hours the solvent was evaporated to dryness. Ethyl acetate was added and the organic portion was washed with saturated sodium bicarbonate solution and brine, dried over anhydrous sodium sulfate and concentrated. Purification with silica gel flash chromatography eluting with a gradient of ethyl acetate (20 to 100%) in hexanes gave the desired compound as a white powder (P-2106, 0.034 g, 34%). MS (ESI) [M+H+]+=451.2.

Workup

  1. customwas evaporated to dryness
  2. additionEthyl acetate was added
  3. washthe organic portion was washed with saturated sodium bicarbonate solution and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customPurification with silica gel flash chromatography
  7. washeluting with a gradient of ethyl acetate (20 to 100%) in hexanes

Sources & evidence

ORD record
ord-229b77aa6f28466abb4c2ea45bb78b31
Source dataset
uspto-grants-2011_01
Patent number
US07872018B2

Reaction notes

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