Hydrochloric Acid → DG-041

HRID 2106067ノート

反応式

HRID 2106067 の反応式
[Cl:1][C:2]1[CH:24]=[C:23]([Cl:25])[CH:22]=[CH:21][C:3]=1[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([F:19])=[CH:11][C:12]=2/[CH:14]=[CH:15]/[C:16](O)=[O:17])[C:7]([CH3:20])=[CH:6]1.CCN=C=NCCCN(C)C.C1C=C2N=NN(O)C2=CC=1.O.C(N(C(C)C)CC)(C)C.[Cl:57][C:58]1[CH:59]=[C:60]([S:64]([NH2:67])(=[O:66])=[O:65])[S:61][C:62]=1[Cl:63].Cl>ClCCl.O>[Cl:1][C:2]1[CH:24]=[C:23]([Cl:25])[CH:22]=[CH:21][C:3]=1[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([F:19])=[CH:11][C:12]=2/[CH:14]=[CH:15]/[C:16]([NH:67][S:64]([C:60]2[S:61][C:62]([Cl:63])=[C:58]([Cl:57])[CH:59]=2)(=[O:65])=[O:66])=[O:17])[C:7]([CH3:20])=[CH:6]1

参加物

9

反応物 6

HCID 313Hydrochloric AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 37220944,5-Dichlorothiophene-2-sulfonamideHCID 57810473HCID 57810473、化合物

生成物 1

HCID 11296282DG-041収率 60%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒

実験手順

To a solution of (E)-3-[1-(2,4-dichloro-benzyl)-5-fluoro-3-methyl-1H-indol-7-yl]-acrylic acid (10.0 g, 26.4 mmol) in dichloromethane (100 mL) was added EDCI (7.9 g, 41.2 mmol), HOBt hydrate (0.71 g, 5.3 mmol), and diisopropylethylamine (10.6 g, 81.8 mmol), and the mixture was stirred for 20 mm. To the reaction was added 4,5-dichlorothiophene-2-sulfonamide (6.43 g, 27.2 mmol), and the mixture was stirred at room temperature for 15 mm, then at reflux for 16 h. The reaction was cooled to room temperature then diluted with 25 mL water followed by 25 mL 2 M HCl. The mixture was stirred for 5 mm, then the phases were split. The organic phase was diluted with 25 mL of 2 M HCl and stirred, which induced precipitation of the product. The temperature was reduced to 0° C., and stirring was continued for 1 h. The product was collected via vacuum filtration, washed with water (3×25 mL) and heptanes (2×25 mL), then vacuum dried at 60° C. to afford 9.3 g (60% yield) of the title compound. The product could be further purified via recrystallization from ethanol: 1H-NMR (400 MHz, DMSO-d6) δ 2.26 (s, 3H), 5.53 (s, 2H), 6.12 (d, 1H, J=8.4 Hz), 6.21 (d, 1H, J=15.4 Hz), 7.04 (dd, 1H, J=10.0, 2.4 Hz), 7.22 (dd, 1H, J=8.4, 2.0 Hz), 7.37 (s, 1H), 7.38 (d, 1H, J=2.0 Hz), 7.46 (dd, 1H, J=9.2, 2.4 Hz), 7.74 (d, 1H, J=15.4 Hz), 7.90 (s, 1H).

後処理

  1. stirringthe mixture was stirred at room temperature for 15 mm
  2. temperatureat reflux for 16 h
  3. stirringThe mixture was stirred for 5 mm
  4. customthe phases were split
  5. additionThe organic phase was diluted with 25 mL of 2 M HCl
  6. stirringstirred
  7. customprecipitation of the product
  8. customwas reduced to 0° C.
  9. stirringstirring
  10. filtrationThe product was collected via vacuum filtration
  11. washwashed with water (3×25 mL) and heptanes (2×25 mL)
  12. customvacuum dried at 60° C.

出典と根拠

ORDレコード
ord-7e525d9c5db44a87b8690675e1df7995
出典データセット
uspto-grants-2009_08
特許番号
US07579483B2

反応ノート

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