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

HRID 1627160

반응식

HRID 1627160 반응식
[Cl-].[Li+].[CH:3]([O-:5])=[O:4].[Li+].[F:7][C:8]1[CH:13]=[N:12][C:11]2[N:14]([S:18]([C:21]3[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=3)(=[O:20])=[O:19])[CH:15]=[C:16](I)[C:10]=2[C:9]=1[CH:28]=[O:29].C(OC(=O)C)(=O)C.C(N(C(C)C)C(C)C)C>CO.C(Cl)Cl.C(O[Pd]OC(=O)C)(=O)C.CN(C=O)C>[F:7][C:8]1[C:9]([CH:28]=[O:29])=[C:10]2[C:16]([C:3]([OH:5])=[O:4])=[CH:15][N:14]([S:18]([C:21]3[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=3)(=[O:20])=[O:19])[C:11]2=[N:12][CH:13]=1

참가 물질

9

반응물 5

HCID 7918Acetic AnhydrideHCID 81531DiisopropylethylamineHCID 433294Lithium ChlorideHCID 23680280Lithium formateHCID 582934925-fluoro-3-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridine-4-carbaldehyde

생성물 1

HCID 582934835-fluoro-4-formyl-1-tosyl-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acid수율 85.5%

시약·촉매·용매 3

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

반응 조건

온도
56 °C

실험 절차

Lithium chloride (0.472 g, 11.14 mmol) and lithium formate (0.579 g, 11.14 mmol) were combined in a sealable dried tube. DMF (10 mL), 5-fluoro-3-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridine-4-carbaldehyde (1.650 g, 3.71 mmol), acetic anhydride (0.702 mL, 7.43 mmol) and diacetoxypalladium (0.083 g, 0.371 mmol) were added. N-Ethyl-N-isopropylpropan-2-amine (1.294 mL, 7.43 mmol) was added and the mixture was sealed and heated at 56° C. for 3 h. The reaction mixture was taken up in MeOH/DCM (20%) and filtered. The yellow solution was concentrated and the residue was dissolved in MeOH/DCM (10%) and washed with aqueous HCl (0.1N). The aqueous phase was extracted two more times. The organics were combined, dried over MgSO4 and concentrated to an orange oil, which was triturated in ether (300 mL). The precipitate was filtered and dried in vacuo to afford the title compound as light yellow solid (1.15 g, 77%). 1H NMR (400 MHz, DMSO-d6) δ 2.37 (s, 3 H) 7.47 (d, J=8.08 Hz, 2 H) 8.10 (d, J=8.10 Hz, 2 H) 8.54-8.65 (m, 2 H) 10.60 (s, 1 H) 13.45 (br. s., 1 H). [M+H] calc'd for C15H10FIN2O3S, 363; found, 363.4.

후처리

  1. customthe mixture was sealed
  2. filtrationfiltered
  3. concentrationThe yellow solution was concentrated
  4. dissolutionthe residue was dissolved in MeOH/DCM (10%)
  5. washwashed with aqueous HCl (0.1N)
  6. extractionThe aqueous phase was extracted two more times
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated to an orange oil, which
  9. customwas triturated in ether (300 mL)
  10. filtrationThe precipitate was filtered
  11. customdried in vacuo

출처 및 근거

ORD 기록
ord-7363de2ce38542f5a8843e3ae67292ba
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08785429B2

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