Tetrahydrofuran → 1-[5-(2,6-dimethyl-phenyl)-1-(4-isopropyl-phenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]-3-methyl-butan-1-ol

HRID 602542Notes

Reaction equation

HRID 602542 reaction equation
[CH2:1]([C:3]1[CH:8]=[CH:7][CH:6]=[C:5](CC)[C:4]=1[C:11]1[CH:12]=[C:13]2[C:19]([CH:20]=[O:21])=[CH:18][N:17]([C:22]3[CH:27]=[CH:26][C:25]([CH:28]([CH3:30])[CH3:29])=[CH:24][CH:23]=3)[C:14]2=[CH:15][N:16]=1)C.[CH2:31]([Mg]Cl)[CH:32]([CH3:34])[CH3:33].[NH4+].[Cl-].[CH2:39]1COCC1>>[CH3:1][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([CH3:39])[C:4]=1[C:11]1[CH:12]=[C:13]2[C:19]([CH:20]([OH:21])[CH2:31][CH:32]([CH3:34])[CH3:33])=[CH:18][N:17]([C:22]3[CH:27]=[CH:26][C:25]([CH:28]([CH3:29])[CH3:30])=[CH:24][CH:23]=3)[C:14]2=[CH:15][N:16]=1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 86624079HCID 86624079, compoundHCID 178418368HCID 178418368, compound

Product 1

HCID 671523991-[5-(2,6-dimethyl-phenyl)-1-(4-isopropyl-phenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]-3-methyl-butan-1-ol

Conditions

Temperature
-78 °C

Procedure

To a solution of 5-(2,6-diethyl-phenyl)-1-(4-isopropyl-phenyl)-1H-pyrrolo[2,3-c]pyridine-3-carbaldehyde (50 mg, 0.13 mmol, prepared by the procedure described in Example 11, Step 3) in THF (2 mL) at −78° C., iso-butylmagnesium chloride (1M solution in THF, 300 μL, 0.32 mmol) is added. The mixture is stirred at −78° C. for two hours and is subsequently allowed to warm to room temperature. A saturated aqueous NH4Cl solution (5 mL) is added, and THF is removed under reduced pressure. The product is extracted with EtOAc. The combined organic extracts are washed with brine, dried over Na2SO4, and concentrated under reduced pressure. Chromatography of the residue affords 1-[5-(2,6-dimethyl-phenyl)-1-(4-isopropyl-phenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]-3-methyl-butan-1-ol as colorless oil. 1H NMR: (CDCl3) 8.97 (s, 1H), 7.64 (s, 1H), 7.9 (s, 1H), 7.48 (d, J=120 Hz, 2H), 7.41 (d, J=10 Hz, 2H), 7.29 (t, J=10 Hz, 1H), 7.15 (d, J=12 Hz, 2H), 5.13 (m, 1H), 3.95 (m, 1H), 2.44 (m, 4H), 1.34 (d, J=14 Hz, 6H), 1.04 (t, J=10 Hz, 6H); LCMS m/z 455.34 (2.58 min).

Workup

  1. customat −78° C.
  2. temperatureto warm to room temperature
  3. customTHF is removed under reduced pressure
  4. extractionThe product is extracted with EtOAc
  5. washThe combined organic extracts are washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-7fcf7ee75d784288916e4c28eea30789
Source dataset
uspto-grants-2011_03
Patent number
US07906528B2

Reaction notes

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