Tetrahydrofuran → 3-[1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-propan-2-ol

HRID 549045Notes

Reaction equation

HRID 549045 reaction equation
[CH2:1]([O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([CH3:14])[CH:9]=[C:8]2[C:15]1[N:23]([S:24]([C:27]2[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=2)(=[O:26])=[O:25])[C:18]2=[N:19][CH:20]=[CH:21][CH:22]=[C:17]2[CH:16]=1)[CH:2]=[CH2:3].[O:34]1CCCC1>C(O)C.[OH-].[K+].OO>[CH3:14][N:10]1[C:11]2[C:7](=[CH:6][C:5]([O:4][CH2:1][CH2:2][CH2:3][OH:34])=[CH:13][CH:12]=2)[C:8]([C:15]2[N:23]([S:24]([C:27]3[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=3)(=[O:26])=[O:25])[C:18]3=[N:19][CH:20]=[CH:21][CH:22]=[C:17]3[CH:16]=2)=[CH:9]1.[CH3:14][N:10]1[C:11]2[C:7](=[CH:6][C:5]([O:4][CH2:1][CH:2]([OH:34])[CH3:3])=[CH:13][CH:12]=2)[C:8]([C:15]2[N:23]([S:24]([C:27]3[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=3)(=[O:26])=[O:25])[C:18]3=[N:19][CH:20]=[CH:21][CH:22]=[C:17]3[CH:16]=2)=[CH:9]1

Participants

7

Reactant 2

HCID 8028Tetrahydrofuran2×HCID 224774022-(5-allyloxy-1-methyl-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine

Product 2

HCID 224772543-[1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-propan-2-olHCID 224773673-{1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-propan-1-ol

Reagents, catalysts & solvents 3

HCID 702EthanolCatalystHCID 784Hydrogen PeroxideCatalystHCID 14797Potassium HydroxideCatalyst

Procedure

A solution of 2-(5-allyloxy-1-methyl-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine [91 mg, Reference Example 15(a)] in dry tetrahydrofuran (5 mL) was treated with a solution of borane-tetrahydrofuran complex in tetrahydrofuran (1200 μl, 1.0M). After stirring at ambient temperature for 7 hours the reaction mixture was treated with ethanol (9 drops), 5N potassium hydroxide (4 drops) and hydrogen peroxide (6 drops) and stirring was continued for 12 hours during which time a white solid was precipitated. The reaction mixture was diluted with water (50 mL) and the pH of this mixture was adjusted to 10 by addition of potassium hydroxide solution (1M) before exhaustively extracting with ethyl acetate. The combined organic extracts were dried over sodium sulfate then evaporated. The residue was subjected to flash column chromatography on silica eluting with a mixture of ethyl acetate and pentane (2:1, v/v) to give 3-{1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-propan-1-ol (50 mg) as a colourless solid [TLC: RF=0.15 (ethyl acetate). MS: 476 (MH+)] and 3-{1-methyl-3-[1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-indol-5-yloxy}-propan-2-ol (8 mg) as a colourless solid. [TLC: RF=0.3 (ethyl acetate); MS: 476 (MH+)].

Workup

  1. stirringstirring
  2. waitwas continued for 12 hours during which time
  3. customa white solid was precipitated
  4. additionThe reaction mixture was diluted with water (50 mL)
  5. additionthe pH of this mixture was adjusted to 10 by addition of potassium hydroxide solution (1M)
  6. extractionbefore exhaustively extracting with ethyl acetate
  7. dry with materialThe combined organic extracts were dried over sodium sulfate
  8. customthen evaporated
  9. additionThe residue was subjected to flash column chromatography on silica eluting with a mixture of ethyl acetate and pentane (2:1

Sources & evidence

ORD record
ord-745a77d7164d4d4a9dedfca920512d1f
Source dataset
uspto-grants-2011_05
Patent number
US07943616B2

Reaction notes

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