Acetonitrile → 3-(3-furan-3-yl-1H-pyrrolo[2,3-b]pyridine-5-yl)-phenol

HRID 603050Notes

Reaction equation

HRID 603050 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.[O:38]1[CH:42]=[CH:41][C:40](B(O)O)=[CH:39]1.C(#N)C.C(=O)([O-])[O-].[Na+].[Na+]>O.CN(C=O)C.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>[O:38]1[CH:42]=[CH:41][C:40]([C:2]2[C:10]3[C:5](=[N:6][CH:7]=[C:8]([C:11]4[CH:12]=[C:13]([OH:17])[CH:14]=[CH:15][CH:16]=4)[CH:9]=3)[NH:4][CH:3]=2)=[CH:39]1

Participants

8

Reactant 4

HCID 6342AcetonitrileHCID 10340Sodium CarbonateHCID 2734358Furan-3-boronic acidHCID 59699703toluene-4-sulfonic acid 3-[3-iodo-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine-5-yl]-phenyl ester

Product 1

HCID 160392353-(3-furan-3-yl-1H-pyrrolo[2,3-b]pyridine-5-yl)-phenolYield 56%

Reagents, catalysts & solvents 3

HCID 178418903HCID 178418903, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

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, prepared method 6), furan-3-boronic acid (11 mg, 0.1 mmol) and dichlorobis (triphenylphosphino)palladium (ii) (3 mg, 0.0046 mmol) in a Smith process vial was added 0.6 mL of a 1:1 mixture of acetonitrile, and a 2 M solution of sodium carbonate in water. The reaction was run in a Personal Chemistry® microwave reactor at 165° C. for 1200 s. The mixture was diluted with DMF (ca. 5 mL) and filtered with a syringe filter (0.45 micron). The filtrate was concentrated in vacuo and redissolved in DMSO. Purification by reverse phase chromatography using a gradient of H2O and acetonitrile (with 0.1% formic acid as a modifier) afforded 3-(3-furan-3-yl-1H-pyrrolo[2,3-b]pyridine-5-yl)-phenol as an off-white solid (6 mg, 56% yield), 1H NMR (500 MHz, DMSO d6) δ 6.70 (dd, J=2.5, 8.0 Hz, 1H), 6.92 (d, J=2.0 Hz, 1H), 7.07 (t, J=2.0 Hz, 1H), 7.13 (d, J=8.0 Hz, 1H), 7.21 (t, J=8.0 Hz, 1H), 7.67 (t, J=1.5 Hz, 1H), 7.77 (d, J=2.5 Hz, 1H), 8.25 (d, J=2.0 Hz, 1H), 8.27 (s, 1H), 8.41 (d, J=2.0 Hz, 1H), 9.5 (broad s, 1H), 11.8 (3, 1H). MS: m/z 277 (M+H+).

Workup

  1. filtrationfiltered with a syringe
  2. filtrationfilter (0.45 micron)
  3. concentrationThe filtrate was concentrated in vacuo
  4. dissolutionredissolved in DMSO
  5. customPurification by reverse phase chromatography

Sources & evidence

ORD record
ord-e05ee2bada6a423fa59ca7003a33d6f3
Source dataset
uspto-grants-2011_03
Patent number
US07906648B2

Reaction notes

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