Acetic Anhydride → 5-chloro-4-formyl-1-tosyl-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acid

HRID 1627136Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1627136
[Cl-].[Li+].O.[CH:4]([O-:6])=[O:5].[Li+].[Cl:8][C:9]1[CH:14]=[N:13][C:12]2[N:15]([S:19]([C:22]3[CH:28]=[CH:27][C:25]([CH3:26])=[CH:24][CH:23]=3)(=[O:21])=[O:20])[CH:16]=[C:17](I)[C:11]=2[C:10]=1[CH:29]=[O:30].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>[Cl:8][C:9]1[C:10]([CH:29]=[O:30])=[C:11]2[C:17]([C:4]([OH:6])=[O:5])=[CH:16][N:15]([S:19]([C:22]3[CH:28]=[CH:27][C:25]([CH3:26])=[CH:24][CH:23]=3)(=[O:21])=[O:20])[C:12]2=[N:13][CH:14]=1

Komponenten

9

Edukt 5

HCID 7918Acetic AnhydrideHCID 81531DiisopropylethylamineHCID 433294Lithium ChlorideHCID 23702287Lithium formate monohydrateHCID 582934415-chloro-3-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridine-4-carbaldehyde

Produkt 1

HCID 582934935-chloro-4-formyl-1-tosyl-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acidAusbeute 75 %

Reagenzien, Katalysatoren, Lösungsmittel 3

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

Reaktionsbedingungen

Temperatur
52 °C

Versuchsvorschrift

Lithium chloride (1.05 g, 24.7 mmol) and lithium formate monohydrate (1.73 g, 24.7 mmol) were combined in a dry sealable tube under nitrogen. DMF (20 mL), 5-chloro-3-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridine-4-carbaldehyde (3.8 g, 8.25 mmol), acetic anhydride (1.56 mL, 16.5 mmol) and palladium acetate (185 mg, 0.83 mmol) were added. DIPEA (2.87 mL) was added, and the reaction tube was sealed and heated at 52° C. for 3 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 with MeOH/DCM (10%, 2×). 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 light tan solid (2.34 g, 75%). 1H NMR (500 MHz, CD3OD) δ 3.15 (s, 3H), 8.24 (d, J=8.5 Hz, 2H), 8.81 (d, J=8.5 Hz, 2H), 9.17 (s, 1H), 9.38 (s, 1H), 11.81 (s, 1H). [M+H] calc'd for C16H11ClN2O5S, 379, 381; found, 379, 381.

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 with MeOH/DCM (10%, 2×)
  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-e37a93263e8c4f1b96636439c82eaacc
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08785429B2

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