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

HRID 1968232Notes

Reaction equation

HRID 1968232 reaction equation
[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

Participants

9

Reactant 5

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
52 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-b3d0ccb442b04219acf0d40b4015adb6
Source dataset
uspto-grants-2013_04
Patent number
US08420816B2

Reaction notes

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