Acetic Acid → HCID 59699973, compound

HRID 901400Notes

Reaction equation

HRID 901400 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9]C)[C:4]=1[C:11]1[C:19]2[C:14](=[N:15][CH:16]=[C:17]([C:20]3[CH:21]=[C:22]([OH:26])[CH:23]=[CH:24][CH:25]=3)[CH:18]=2)[NH:13][CH:12]=1.BrBr.[OH-].[K+].Cl.[CH3:32][C:33]([OH:35])=O>>[OH:9][C:5]1[C:4]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[C:17]([C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([OH:26])[CH:21]=4)[CH:18]=3)[NH:13][CH:12]=2)=[C:3]([O:2][CH3:1])[CH:8]=[CH:7][C:6]=1[C:33](=[O:35])[CH3:32]

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 24408BromineHCID 59699929HCID 59699929, compound

Product 1

HCID 59699973HCID 59699973, compoundYield 20%

Conditions

Temperature
70 °C

Procedure

To 3-[3-(2,6-dimethoxy-phenyl)-1H-pyrrolo[2,3-b]pyridine-5-yl]-phenol (12 mg, 0.0346 mmol) was added 0.5 mL of 33 wt % bromine in AcOH. The mixture was stirred at 70° C. for 6 h, then it was treated with 1.2 mL 50 wt % of aqueous KOH and it was further stirred at room temperature for 3 days, then at 80° C. for 3 hours. The mixture was acidified to pH 4 with 1N aqueous HCl and extracted with EtOAc three times. The extracts were combined and adsorbed on silica gel. Purification on silica gel with a gradient of methanol/dichloromethane afforded 1-{2-hydroxy-3-[5-(3-hydroxy-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-yl]-4-methoxy-phenyl}-ethanone as a white solid (2.6 mg, 20% yield). 1H NMR (500 MHz, DMSO-d6) δ 2.65 (s, 3H), 3.85 (s, 3H), 6.72 (dd, J=2.5, 8.5 Hz, 1H), 6.83 (d, J=8.5 Hz, 1H), 6.99 (t, J=2.0 Hz, 1H), 7.05 (d, J=8.0 Hz, 1H), 7.23 (t, J=8.0 Hz, 1H), 7.54 (d, J=2.5 Hz, 1H), 7.73 (d, J=2.0 Hz, 1H), 8.00 (d, J=9.0 Hz, 1H), 8.44 (d, J=2.0 Hz, 1H), 9.49 (s, 1H), 11.9 (s, 1H), 13.0 (s, 1H). MS: m/z 375 (M+H+).

Workup

  1. stirringwas further stirred at room temperature for 3 days
  2. waitat 80° C. for 3 hours
  3. extractionextracted with EtOAc three times
  4. customPurification on silica gel with a gradient of methanol/dichloromethane

Sources & evidence

ORD record
ord-259e88e666a44026b8e3a845bf83a677
Source dataset
uspto-grants-2008_04
Patent number
US07361763B2

Reaction notes

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