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

HRID 1627186노트

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HRID 1627186 반응식
[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]

참가 물질

9

반응물 5

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

생성물 1

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

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 6228Dimethylformamide용매HCID 21226129Dichloromethane methanol용매

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온도
56 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-fbac4298fb5c40a7a53fddc940f863da
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08785429B2

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