Diisopropylamine → 1h-Pyrrolo[2,3-c]pyridine-2-methanol,a-3-furanyl-1-(phenylsulfonyl)-

HRID 1821904Notes

Reaction equation

HRID 1821904 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[C:13]1([S:19]([N:22]2[C:26]3=[CH:27][N:28]=[CH:29][CH:30]=[C:25]3[CH:24]=[CH:23]2)(=[O:21])=[O:20])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.CN(C)CCN(C)C.[CH:39]1[C:43]([CH:44]=[O:45])=[CH:42][O:41][CH:40]=1.[Cl-].[NH4+]>O1CCCC1>[O:41]1[CH:40]=[CH:39][C:43]([CH:44]([C:23]2[N:22]([S:19]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)(=[O:21])=[O:20])[C:26]3=[CH:27][N:28]=[CH:29][CH:30]=[C:25]3[CH:24]=2)[OH:45])=[CH:42]1

Participants

8

Reactant 6

HCID 7912DiisopropylamineHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 103513-FuraldehydeHCID 25517Ammonium ChlorideHCID 595812711-(Phenylsulfonyl)-1H-pyrrolo[2,3-c]pyridineHCID 178418339Butyllithium

Product 1

HCID 689805421h-Pyrrolo[2,3-c]pyridine-2-methanol,a-3-furanyl-1-(phenylsulfonyl)-Yield 38%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

A solution of diisopropylamine (0.43 mL, 3.07 mmol) in tetrahydrofuran (4 mL) was cooled to −78° C. under a nitrogen atmosphere. n-Butyllithium (1.24 mL of a 2.5 M solution in hexanes) was added dropwise and the reaction mixture was stirred for 30 minutes at −78° C. and then warmed to −30° C. A solution of 1-(phenylsulfonyl)-1H-pyrrolo[2,3-c]pyridine (Reference Example 12) (400 mg, 1.55 mmol) and N,N,N′,N′-tetramethylethylenediamine (0.24 mL, 1.59 mmol) in tetrahydrofuran (4 mL) was added and the reaction mixture was stirred for 45 minutes. A solution of 3-furfural (0.27 mL, 3.12 mmol) in tetrahydrofuran (3 mL) was added dropwise. The reaction mixture was allowed to warm to ambient temperature over 2 h. Saturated ammonium chloride solution (5 mL) was added to quench the reaction mixture. The reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate (3×25 mL). The combined organic extracts were washed successively with water and brine, dried over sodium sulfate and concentrated to dryness. Recrystallization from methanol gave 3-furyl[1-(phenylsulfonyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]methanol (208 mg, 38%) as an off-white solid: mp 168-171° C.; 1H NMR (500 MHz, DMSO-d6) δ 6.24 (1H, d, J=5.8 Hz), 6.40 (1H, d, J=5.8 Hz), 6.48 (1H, d, J=1.1 Hz), 6.84 (1H, s), 7.55-7.62 (5H, m), 7.68-7.71 (1H, m), 7.92-7.94 (2H, m), 8.35 (1H, d, J=5.2 Hz), 9.23 (1H, s); ESI MS m/z 355 [C18H14N2O4S+H]+; HPLC (Method A) >99% (AUC), tR=15.4 min.

Workup

  1. temperaturewarmed to −30° C
  2. stirringthe reaction mixture was stirred for 45 minutes
  3. temperatureto warm to ambient temperature over 2 h
  4. customto quench the reaction mixture
  5. additionThe reaction mixture was diluted with water (10 mL)
  6. extractionextracted with ethyl acetate (3×25 mL)
  7. washThe combined organic extracts were washed successively with water and brine
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated to dryness
  10. customRecrystallization from methanol

Sources & evidence

ORD record
ord-094d5dcab899407d94e825fd5764f0b6
Source dataset
uspto-grants-2009_10
Patent number
US07608627B2

Reaction notes

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