Thionyl Chloride → 3-(6-hydroxy-1,3-benzodioxol-5-yl)-1-pentyl-1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one

HRID 1715209Notes

Reaction equation

HRID 1715209 reaction equation
O[C:2]1([C:17]2[C:25]([OH:26])=[CH:24][C:20]3[O:21][CH2:22][O:23][C:19]=3[CH:18]=2)[C:10]2[C:5](=[N:6][CH:7]=[CH:8][CH:9]=2)[N:4]([CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])[C:3]1=[O:16].C(N(C(C)C)CC)(C)C.S(Cl)(Cl)=O>ClCCl.[Zn]>[OH:26][C:25]1[C:17]([CH:2]2[C:10]3[C:5](=[N:6][CH:7]=[CH:8][CH:9]=3)[N:4]([CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])[C:3]2=[O:16])=[CH:18][C:19]2[O:23][CH2:22][O:21][C:20]=2[CH:24]=1

Participants

6

Reactant 3

HCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 119627703-hydroxy-3-(6-hydroxy-1,3-benzodioxol-5-yl)-1-pentyl-1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one

Product 1

HCID 119627743-(6-hydroxy-1,3-benzodioxol-5-yl)-1-pentyl-1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-oneYield 76.6%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-hydroxy-3-(6-hydroxy-1,3-benzodioxol-5-yl)-1-pentyl-1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one (4.00 g, 11.2 mmol) in anhydrous dichloromethane (80.0 mL) was added diisopropylethylamine (6.10 mL) and thionyl chloride (2.77 g, 23.5 mmol) under nitrogen at 0° C. The reaction mixture was stirred at 0° C. for 1 h and concentrated in vacuo to dryness. The residue was dissolved in THF/acetic acid (7:3, 100 mL) followed by the addition of Zn dust (3.08 g, 47.1 mmol) in one portion. The reaction mixture was stirred at ambient temperature for 16 h, filtered and the residue was washed with ethyl acetate (30.0 mL). The filtrate was concentrated in vacuo to dryness. The residue was dissolved in ethyl acetate (200 mL), washed with saturated ammonium chloride (3×50.0 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness. The residue was subjected to column chromatography to give the title compound (2.92 g, 76%): 1H NMR (300 MHz, CDCl3) δ 8.64 (br, 1H), 8.26 (d, 1H), 7.52 (d, 1H), 7.05 (dd, 1H), 6.53 (s, 1H), 6.25 (s, 1H), 5.84 (d, 2H), 5.02 (s, 1H), 3.86-3.75 (m, 2H), 1.76-1.67 (m, 2H), 1.33-1.28 (m, 4H), 0.85 (t, 3H); 13C NMR (75 MHz, CDCl3) δ 178.5, 157.4, 150.9, 147.8, 147.5, 141.6, 133.2, 121.7, 118.7, 114.1, 106.4, 101.2, 101.1, 46.5, 39.8, 28.9, 27.3, 22.3, 13.9; MS (ES+) m/z 341 (M+1).

Workup

  1. concentrationconcentrated in vacuo to dryness
  2. dissolutionThe residue was dissolved in THF/acetic acid (7:3, 100 mL)
  3. stirringThe reaction mixture was stirred at ambient temperature for 16 h
  4. filtrationfiltered
  5. washthe residue was washed with ethyl acetate (30.0 mL)
  6. concentrationThe filtrate was concentrated in vacuo to dryness
  7. dissolutionThe residue was dissolved in ethyl acetate (200 mL)
  8. washwashed with saturated ammonium chloride (3×50.0 mL)
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationThe filtrate was concentrated in vacuo to dryness

Sources & evidence

ORD record
ord-1aa4e17771824102a7ebde8bd7563b09
Source dataset
uspto-grants-2010_09
Patent number
US07799798B2

Reaction notes

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