Trifluoroacetic acid → HCID 178492384, Verbindung

HRID 343231Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 343231
FC(F)(F)C(O)=O.[F:8][C:9]1[CH:59]=[CH:58][C:12]2[N:13]([CH2:43][C:44]([N:46]([CH:55]([CH3:57])[CH3:56])[C:47]3[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[CH:49][CH:48]=3)=[O:45])[C:14](=[O:42])[CH:15]([CH2:25][C:26]3[C:34]4[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=4)[N:28](C(OC(C)(C)C)=O)[N:27]=3)[C:16](=[O:24])[N:17]([C:18]3[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=3)[C:11]=2[CH:10]=1>>[F:8][C:9]1[CH:59]=[CH:58][C:12]2[N:13]([CH2:43][C:44]([N:46]([CH:55]([CH3:57])[CH3:56])[C:47]3[CH:48]=[CH:49][C:50]([O:53][CH3:54])=[CH:51][CH:52]=3)=[O:45])[C:14](=[O:42])[CH:15]([CH2:25][C:26]3[C:34]4[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=4)[NH:28][N:27]=3)[C:16](=[O:24])[N:17]([C:18]3[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=3)[C:11]=2[CH:10]=1

Komponenten

3

Edukt 2

HCID 6422Trifluoroacetic acidHCID 867535912-[7-Fluoro-3-(1-tert-butoxycarbonyl-indazol-3-ylmethyl)-2,4-dioxo-5-pyridin-3-yl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-(4-methoxy-phenyl)-acetamide

Produkt 1

HCID 178492384HCID 178492384, VerbindungAusbeute 91,5 %

Versuchsvorschrift

To a solution of 5 mL of trifluoroacetic acid under nitrogen is add 364 mg of 2-[7-fluoro-3-(1-tertbutoxycarbonyl-indazol-3-ylmethyl)-2,4-dioxo-5-pyridin-3-yl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-(4-methoxy-phenyl)-acetamide, prepared as in Intermediate 66. After stirring at ambient temperature for 20 min, the reaction mixture is evaporated in vacuo and the residue is partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The layers were separated and the aqueous layer is back-extracted with dichloromethane. The organic layers were combined, washed with aqueous sodium hydroxide (1N), dried over anhydrous sodium sulfate, filtered and evaporated in vacuo. The residue is triturated with hexane, the hexane is removed in vacuo, and the residual solid is dried under high vacuum to provide 286 mg of the title compound as a white solid: 1H NMR (300 MHz, CDCl3) δ8.67 (s, br, 1H), 8.56 (dd, 1H, J=1.5, 5.2), 8.10 (d, 1H, J=8.1), 7.82 (d, 1H, J=8.1), 7.52 (dd, 1H, J=5.3, 8.3), 7.35 (m, 3H), 7.14 (m, 3H), 7.03 (m, 1H), 6.96 (m, 3H), 6.61 (dd, 1H, J=2.7, 8.9), 4.92 (m, 1H), 4.51 (d, 1H, J=15.8), 4.29 (dd, 1H, J=5.8, 7.7), 4.05 (d, 1H, J=16.0), 3.84 (s, 3H), 3.78 (dd, 1H, J=7.8, 16.4), 3.61 (dd, 1H, J=5.9, 16.2), 1.03 (d, 6H, J=6.8); low resolution MS (FAB)m/e 607 (MH+).

Aufarbeitung

  1. customthe reaction mixture is evaporated in vacuo
  2. customthe residue is partitioned between ethyl acetate and saturated aqueous sodium bicarbonate
  3. customThe layers were separated
  4. extractionthe aqueous layer is back-extracted with dichloromethane
  5. washwashed with aqueous sodium hydroxide (1N)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe residue is triturated with hexane
  10. customthe hexane is removed in vacuo
  11. customthe residual solid is dried under high vacuum

Quellen und Nachweise

ORD-Eintrag
ord-ed0f04f56f0047c7961ef639e9ef8d29
Quelldatensatz
uspto-grants-1999_01
Patentnummer
US05859007

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