Acetic Anhydride → 4-Formyl-1-tosyl-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acid

HRID 1627186Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1627186
[Cl-].[Li+].O.[CH:4]([O-:6])=[O:5].[Li+].I[C:9]1[C:17]2[C:16]([CH:18]=[O:19])=[CH:15][CH:14]=[N:13][C:12]=2[N:11]([S:20]([C:23]2[CH:29]=[CH:28][C:26]([CH3:27])=[CH:25][CH:24]=2)(=[O:22])=[O:21])[CH:10]=1.C(OC(=O)C)(=O)C.CCN(C(C)C)C(C)C>CO.C(Cl)Cl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C=O)C>[CH:18]([C:16]1[CH:15]=[CH:14][N:13]=[C:12]2[N:11]([S:20]([C:23]3[CH:29]=[CH:28][C:26]([CH3:27])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[CH:10]=[C:9]([C:4]([OH:6])=[O:5])[C:17]=12)=[O:19]

Komponenten

9

Edukt 5

HCID 7918Acetic AnhydrideHCID 81531DiisopropylethylamineHCID 433294Lithium ChlorideHCID 23702287Lithium formate monohydrateHCID 582934163-Iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridine-4-carbaldehyde

Produkt 1

HCID 582934364-Formyl-1-tosyl-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acidAusbeute 89,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 6228DimethylformamideLösungsmittelHCID 21226129Dichloromethane methanolLösungsmittel

Reaktionsbedingungen

Temperatur
56 °C

Versuchsvorschrift

Lithium chloride (358 mg, 8.45 mmol) and lithium formate monohydrate (591 mg, 8.45 mmol) were combined in a dry sealable tube under nitrogen. DMF (12 mL), 3-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridine-4-carbaldehyde (1.2 g, 2.82 mmol), acetic anhydride (532 mL, 5.63 mmol) and palladium acetate (63 mg, 0.28 mmol) were added. DIPEA (981 μL) was added, and the reaction tube was sealed and heated at 56° C. for 4 h. The reaction mixture was taken up in MeOH/DCM (20%) and filtered to remove the insoluble black carbon material. The yellow solution was concentrated in vacuo, dissolved in MeOH/DCM (10%), and washed with aqueous HCl (0.1N). The aqueous layer was extracted twice with MeOH/DCM (10%). The organics were combined, dried over MgSO4, and concentrated in vacuo. Purification by silica gel chromatography (10-15% MeOH/DCM) gave the title compound as a tan solid (866 mg, 89%). 1H NMR (500 MHz, DMSO-d6) δ 2.35 (s, 3H), 7.45 (d, J=8.5 Hz, 2H), 7.62 (d, J=5.0 Hz, 1H), 8.11 (d, J=8.5 Hz, 2H), 8.58-8.62 (m, 2H), 11.02 (s, 1H), 13.20 (br s, 1H). [M+H] calc'd for C16H12N2O5S, 345; found, 345.

Aufarbeitung

  1. customthe reaction tube was sealed
  2. filtrationfiltered
  3. customto remove the insoluble black carbon material
  4. concentrationThe yellow solution was concentrated in vacuo
  5. dissolutiondissolved in MeOH/DCM (10%)
  6. washwashed with aqueous HCl (0.1N)
  7. extractionThe aqueous layer was extracted twice with MeOH/DCM (10%)
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated in vacuo
  10. customPurification by silica gel chromatography (10-15% MeOH/DCM)

Quellen und Nachweise

ORD-Eintrag
ord-fbac4298fb5c40a7a53fddc940f863da
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08785429B2

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