Acetonitrile → 5-[5-(3,4-dimethoxyphenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-pyridin-2-ol

HRID 901536Notes

Reaction equation

HRID 901536 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[CH:12]=[CH:13][C:14]([OH:17])=[N:15][CH:16]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[CH3:18][O:19][C:20]1[CH:21]=[C:22](B(O)O)[CH:23]=[CH:24][C:25]=1[O:26][CH3:27].C(#N)C.C(=O)([O-])[O-].[Na+].[Na+]>O.Cl[Pd-2](Cl)(P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:18][O:19][C:20]1[CH:21]=[C:22]([C:2]2[CH:3]=[C:4]3[C:10]([C:11]4[CH:12]=[CH:13][C:14]([OH:17])=[N:15][CH:16]=4)=[CH:9][NH:8][C:5]3=[N:6][CH:7]=2)[CH:23]=[CH:24][C:25]=1[O:26][CH3:27]

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 10340Sodium CarbonateHCID 27347023,4-Dimethoxyphenylboronic acidHCID 178515884HCID 178515884, compound

Product 1

HCID 1784887425-[5-(3,4-dimethoxyphenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-pyridin-2-olYield 34%

Reagents, catalysts & solvents 2

HCID 178418903HCID 178418903, compoundCatalystHCID 962WaterSolvent2×

Procedure

To 5-(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-pyridin-2-ol, 3,4-dimethoxyphenyl boronic acid (1.3 equiv.) and dichlorobis (triphenylphosphino)palladium (ii) (6 mol %) in a Smith process vial was added a 3:2:1 mixture of acetonitrile, water, and a 2 M solution of sodium carbonate in water to achieve an overall concentration of the starting material of 0.10 M. The reaction was run in a Personal Chemistry® microwave reactor at 165° C. for 1200 s. Water was added and the mixture extracted three times with ethyl acetate. Purification on silica gel with a gradient of MeOH/CH2Cl2 afforded 5-[5-(3,4-dimethoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-pyridin-2-ol as an off-white solid (34% yield). 1H NMR (DMSO-d6): δ 11.86 (broad s, 1H), 11.67 (broad s, 1H), 8.52 (d, J=2.0 Hz, 1H), 8.22 (d, J=2.0 Hz, 1H), 7.89 (dd, J=2.5, 10 Hz, 1H), 7.75 (s, 1H), 7.73 (s, 1H), 7.29 (d, J=2.0 Hz, 1H), 7.23 (dd, J=2.0, 8.0 Hz, 1H), 7.04 (d, J=8.5 Hz, 1H), 6.44 (d, J=9.0 Hz, 1H), 3.85 (s, 3H), 3.79 (s, 3H); MS: m/z 348.1 [MH]+.

Workup

  1. concentrationan overall concentration of the starting material of 0.10 M
  2. additionWater was added
  3. extractionthe mixture extracted three times with ethyl acetate
  4. customPurification on silica gel with a gradient of MeOH/CH2Cl2

Sources & evidence

ORD record
ord-66354f49e8b745f0b9ba9603353be5dc
Source dataset
uspto-grants-2008_04
Patent number
US07361764B2

Reaction notes

Loading…