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

HRID 1627160ノート

反応式

HRID 1627160 の反応式
[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

参加物

9

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 6228Dimethylformamide溶媒HCID 21226129Dichloromethane methanol溶媒

反応条件

温度
56 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-7363de2ce38542f5a8843e3ae67292ba
出典データセット
uspto-grants-2014_07
特許番号
US08785429B2

反応ノート

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