2-Vinylpyridine → 3-{3-[2-(Pyridin-2-yl)ethenyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}phenol

HRID 1820059Notes

Reaction equation

HRID 1820059 reaction equation
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([C:11]3[CH:12]=[C:13]([O:17]S(C4C=CC(C)=CC=4)(=O)=O)[CH:14]=[CH:15][CH:16]=3)[CH:9]=2)[N:4](S(C2C=CC(C)=CC=2)(=O)=O)[CH:3]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C.[CH:67]([C:69]1[CH:74]=[CH:73][CH:72]=[CH:71][N:70]=1)=[CH2:68]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C=O)C>[N:70]1[CH:71]=[CH:72][CH:73]=[CH:74][C:69]=1[CH:67]=[CH:68][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([C:11]3[CH:12]=[C:13]([OH:17])[CH:14]=[CH:15][CH:16]=3)[CH:9]=2)[NH:4][CH:3]=1

Participants

7

Reactant 4

HCID 75212-VinylpyridineHCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 59699703toluene-4-sulfonic acid 3-[3-iodo-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine-5-yl]-phenyl ester

Product 1

HCID 670612563-{3-[2-(Pyridin-2-yl)ethenyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}phenolYield 70.5%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To toluene-4-sulfonic acid 3-[3-iodo-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine-5-yl]-phenyl ester (50 mg, 0.077 mmol), tri-ortho-tolylphosphine (10 mg, 0.031 mmol), palladium (II) acetate (2 mg, 0.0077 mmol) was added DMF (0.5 mL), triethylamine (32 uL, 0.232 mmol), and 2-vinylpyridine (42 uL, 0.388 mmol). The vial was flushed with nitrogen, and the reaction was run in a Personal Chemistry® microwave reactor at 150° C. for 900 s. Water was added and the mixture was neutralized to pH 6 with 1 N aqueous HCl, then extracted with EtOAc three times. The extracts were combined and concentrated in vacuo. The crude was treated with 1 mL of EtOH and 1 mL of aqueous KOH (50 wt %). The reaction mixture was stirred at 80° C. for 15 h. The mixture was neutralized to pH 7 with 1 N aqueous HCl, and the resulting precipitate was filtered, washed with water, dried in vacuo, and adsorbed on silica gel. Purification on silica gel with a gradient of MeOH/CH2Cl2 afforded 3-[3-(2-pyridin-2-yl-vinyl)-1H-pyrrolo[2,3-b]pyridine-5-yl]-phenol as a yellow solid (17 mg, 35% yield). 1H NMR (500 MHz, DMSO-d6) δ 6.78 (dd, J=2.0, 8.0 Hz, 1H), 7.13 (s, 1H), 7.15-7.20 (m, 2H), 7.26 (d, J=16.0 Hz, 1H), 7.29 (t, J=8.0 Hz, 1H), 7.57 (d, J=7.5 Hz, 1H), 7.73 (dt, J=2.0, 8.0 Hz, 1H), 7.90 (d, J=16.0 Hz, 1H), 7.93 (d, J=2.0 Hz, 1H), 8.50 (d, J=2.0 Hz, 1H), 8.52 (d, J=5.0 Hz, 1H), 8.54 (d, J=2.5 Hz, 1H), 9.56 (s, 1H), 12.1 (s, 1H). MS: m/z 314 (M+H+).

Workup

  1. customThe vial was flushed with nitrogen
  2. additionWater was added
  3. extractionextracted with EtOAc three times
  4. concentrationconcentrated in vacuo
  5. additionThe crude was treated with 1 mL of EtOH and 1 mL of aqueous KOH (50 wt %)
  6. filtrationthe resulting precipitate was filtered
  7. washwashed with water
  8. customdried in vacuo
  9. customPurification on silica gel with a gradient of MeOH/CH2Cl2

Sources & evidence

ORD record
ord-f3d6bc703863409891f8299136511072
Source dataset
uspto-grants-2009_10
Patent number
US07601839B2

Reaction notes

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