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

HRID 1968282Notes

Reaction equation

HRID 1968282 reaction equation
[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]

Participants

9

Reactant 5

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

Product 1

HCID 582934364-Formyl-1-tosyl-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acidYield 89.2%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
56 °C

Procedure

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.

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 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)

Sources & evidence

ORD record
ord-e2218637e05b4c1e9f17ca9648ee2e64
Source dataset
uspto-grants-2013_04
Patent number
US08420816B2

Reaction notes

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