Vorinostat → Octanoic acid, 8-oxo-8-(phenylamino)-, [1,8-dioxo-8-(phenylamino)octyl]azanyl ester

HRID 1516961Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1516961
[C:1]([OH:18])(=[O:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][C:8]([NH:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:9].ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH:41]1[CH:46]=[CH:45][C:44]([NH:47][C:48]([CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][C:56]([NH:58]O)=[O:57])=[O:49])=[CH:43][CH:42]=1>CN(C=O)C>[C:11]1([NH:10][C:8]([CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][C:1]([O:18][NH:58][C:56](=[O:57])[CH2:55][CH2:54][CH2:53][CH2:52][CH2:51][CH2:50][C:48]([NH:47][C:44]2[CH:45]=[CH:46][CH:41]=[CH:42][CH:43]=2)=[O:49])=[O:17])=[O:9])[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Komponenten

6

Edukt 4

HCID 5311VorinostatHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 9543537Suberanilic Acid

Produkt 1

HCID 11518876Octanoic acid, 8-oxo-8-(phenylamino)-, [1,8-dioxo-8-(phenylamino)octyl]azanyl esterAusbeute 77,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

To a stirring solution of suberanilic acid (3.0 g, 12.0 mmol) in DMF (60 mL) was added 1-hydroxybenzotriazole (1.79 g, 13.2 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) (2.54 g, 13.2 mmol). After 5 mins, a solution of SAHA (3.18 g, 12.0 mmol) in DMF (30 mL) was added to the mixture with stirring. After 24 h, the solvent was removed and the residue was triturated with EtOAc (50 mL). The slurry was filtered to yield an off-white solid, which was triturated in CH2Cl2 (50 mL). The slurry was filtered yielding a white solid (4.6 g, 77%). Half of the material was purified further by repeating the washing procedures with an addition of H2O (20 mL) in the EtOAc wash. The white solid was filtered to yield the desired material (2.1 g). MP: 151-153° C. 1H NMR (DMSO-d6) δ 11.51 (s, 1H), 9.82 (s, 2H), 7.54 (d, J=7.9 Hz, 4H), 7.23 (dd, J=7.9, 7.6 Hz, 4H), 6.97 (t, J=7.6 Hz, 2H), 2.39 (t, J=7.2 Hz, 2H), 2.24 (t, J=6.8 Hz, 4H), 1.98 (t, J=6.8 Hz, 2H), 1.66-1.38 (m, 8H), 1.38-1.16 (m, 8H). 13C NMR (DMSO-d6) δ 171.33, 169.94, 139.49, 128.72, 123.02, 119.21, 36.49, 32.02, 31.06, 28.50, 28.37, 28.14, 25.12, 25.05, 24.79, 24.38. MS (EI): cal'd (MH+) 496, exp (MH+) 496.

Aufarbeitung

  1. waitAfter 24 h
  2. customthe solvent was removed
  3. customthe residue was triturated with EtOAc (50 mL)
  4. filtrationThe slurry was filtered
  5. customto yield an off-white solid, which
  6. customwas triturated in CH2Cl2 (50 mL)
  7. filtrationThe slurry was filtered

Quellen und Nachweise

ORD-Eintrag
ord-6bbe59ed88c34b63a1c5c36b1b3a8d31
Quelldatensatz
uspto-grants-2012_07
Patentnummer
US08227636B2

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