1H-pyrrolo[2,3-c]pyridine-2-carbaldehyde → 1h-Pyrrolo[2,3-c]pyridine-2-methanol,a-(4-methylphenyl)-

HRID 1821884Notes

Reaction equation

HRID 1821884 reaction equation
[NH:1]1[C:5]2=[CH:6][N:7]=[CH:8][CH:9]=[C:4]2[CH:3]=[C:2]1[CH:10]=[O:11].[C:12]1([CH3:20])[CH:17]=[CH:16][C:15]([Mg]Br)=[CH:14][CH:13]=1>O1CCCC1>[CH3:20][C:12]1[CH:17]=[CH:16][C:15]([CH:10]([C:2]2[NH:1][C:5]3=[CH:6][N:7]=[CH:8][CH:9]=[C:4]3[CH:3]=2)[OH:11])=[CH:14][CH:13]=1

Participants

4

Reactant 2

HCID 468564601H-pyrrolo[2,3-c]pyridine-2-carbaldehydeHCID 178418370HCID 178418370, compound

Product 1

HCID 578934571h-Pyrrolo[2,3-c]pyridine-2-methanol,a-(4-methylphenyl)-Yield 77%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

1H-pyrrolo[2,3-c]pyridine-2-carboxaldehyde (180 mg, 1.23 mmol) was dissolved in tetrahydrofuran (6 mL) under a nitrogen atmosphere. p-Tolylmagnesium bromide in tetrahydrofuran (2.48 mL, 2.48 mmol) was added dropwise. After stirring for 3 h, the reaction mixture was quenched by pouring into a 2:1 solution of saturated ammonium chloride and water, then extracted with ethyl acetate (2×20 mL). The combined organic extracts were washed with water and then brine, dried over sodium sulfate, and concentrated to provide the crude material. Purification by Biotage chromatography (silica, 0 to 18% methanol in methylene chloride) to provide (4-methylphenyl)(1H-pyrrolo[2,3-c]pyridin-2-yl)methanol (226 mg, 77%) as an off-white solid: mp 78-82° C.; 1H NMR (500 MHz, CD3OD) δ2.32 (3H, s), 5.95 (1H, s), 6.36 (1H, s), 7.17 (2H, d, J=7.9 Hz), 7.34 (2H, d, 8.0 Hz), 7.51 (1H, m), 8.00 (1H, d, J=5.6 Hz), 8.59 (1H, s); ESI MS m/z 239 [C15H14N2+H]+; HPLC (Method A) >99% (AUC), tR=15.1 min.

Workup

  1. customthe reaction mixture was quenched
  2. additionby pouring into a 2:1 solution of saturated ammonium chloride and water
  3. extractionextracted with ethyl acetate (2×20 mL)
  4. washThe combined organic extracts were washed with water
  5. dry with materialbrine, dried over sodium sulfate
  6. concentrationconcentrated
  7. customto provide the crude material
  8. customPurification by Biotage chromatography (silica, 0 to 18% methanol in methylene chloride)

Sources & evidence

ORD record
ord-a8005a8ce0bf46da919d6b7b7a7d63c9
Source dataset
uspto-grants-2009_10
Patent number
US07608627B2

Reaction notes

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