Sodium Hydroxide → 5-Chloro-3-(2-ethoxypyridin-3-yl)-6-fluoro-3-{2-[4-(1-methylpiperidin-4-yl)piperazin-1-yl]-2-oxo-ethyl}-1,3-dihydroindol-2-one

HRID 57203

Reaktionsgleichung

Reaktionsgleichung von HRID 57203
F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[CH3:37][N:38]1[CH2:43][CH2:42][CH:41]([N:44]2[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]2)[CH2:40][CH2:39]1.[Cl:50][C:51]1[CH:52]=[C:53]2[C:57](=[CH:58][C:59]=1[F:60])[NH:56][C:55](=[O:61])[C:54]2([CH2:71][C:72](O)=[O:73])[C:62]1[C:63]([O:68][CH2:69][CH3:70])=[N:64][CH:65]=[CH:66][CH:67]=1.[OH-].[Na+]>ClCCl.C(OCC)(=O)C>[Cl:50][C:51]1[CH:52]=[C:53]2[C:57](=[CH:58][C:59]=1[F:60])[NH:56][C:55](=[O:61])[C:54]2([C:62]1[C:63]([O:68][CH2:69][CH3:70])=[N:64][CH:65]=[CH:66][CH:67]=1)[CH2:71][C:72]([N:47]1[CH2:48][CH2:49][N:44]([CH:41]2[CH2:40][CH2:39][N:38]([CH3:37])[CH2:43][CH2:42]2)[CH2:45][CH2:46]1)=[O:73]

Komponenten

8

Edukt 5

HCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 5663241-(1-Methyl-4-piperidinyl)piperazineHCID 67087607HCID 67087607, Verbindung

Produkt 1

HCID 670875065-Chloro-3-(2-ethoxypyridin-3-yl)-6-fluoro-3-{2-[4-(1-methylpiperidin-4-yl)piperazin-1-yl]-2-oxo-ethyl}-1,3-dihydroindol-2-oneAusbeute 83,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

200 mg (0.45 mmol) of BOP, 1.07 ml (6.17 mmol) of diisopropylethylamine and then 79 mg (0.43 mmol) of 1-(1-methylpiperidin-4-yl)piperazine were added to a solution of 150 mg (0.41 mmol) of [5-chloro-3-(2-ethoxypyridin-3-yl)-6-fluoro-2-oxo-2,3-dihydro-1H-indol-3-yl]acetic acid in 2 ml of dichloromethane. The reaction mixture was stirred at room temperature overnight. 6 ml of a 2-molar NaOH were added to the reaction solution, and it was stirred at room temperature for 15 minutes. The reaction mixture was diluted with ethyl acetate. The phases were separated and the aqueous phase was extracted with ethyl acetate (1×). The combined organic phase was again washed with water (1×) and saturated sodium chloride solution (1×), dried over magnesium sulfate and filtered, and the solvent was evaporated in vacuo. The residue was purified by chromatography on silica gel (Redisep cartridge, mobile phase gradient from 2 to 50% methanol in dichloromethane). 181 mg of the title compound were obtained as a white solid.

Aufarbeitung

  1. stirringwas stirred at room temperature for 15 minutes
  2. customThe phases were separated
  3. extractionthe aqueous phase was extracted with ethyl acetate (1×)
  4. washThe combined organic phase was again washed with water (1×) and saturated sodium chloride solution (1×)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customthe solvent was evaporated in vacuo
  8. customThe residue was purified by chromatography on silica gel (Redisep cartridge, mobile phase gradient from 2 to 50% methanol in dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-62860e21fae94bbca057193259aada9f
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09434713B2

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