Sodium bis(trimethylsilyl)amide → HCID 10841112, Verbindung

HRID 343219Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 343219
[O:1]=[C:2]1[N:8]([CH2:9][C:10]([N:12]([CH:21]([CH3:23])[CH3:22])[C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)=[O:11])[C:7]2[CH:24]=[CH:25][CH:26]=[CH:27][C:6]=2[N:5]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:4](=[O:34])[CH2:3]1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Br[CH2:46][C:47]1[C:51]2[CH:52]=[CH:53][CH:54]=[CH:55][C:50]=2[O:49][N:48]=1>CN(C=O)C.C1COCC1>[O:49]1[C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][C:51]=2[C:47]([CH2:46][CH:3]2[C:2](=[O:1])[N:8]([CH2:9][C:10]([N:12]([CH:21]([CH3:23])[CH3:22])[C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=3)=[O:11])[C:7]3[CH:24]=[CH:25][CH:26]=[CH:27][C:6]=3[N:5]([C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)[C:4]2=[O:34])=[N:48]1

Komponenten

6

Edukt 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 34991891,2-Benzisoxazole, 3-(bromomethyl)-HCID 107900232-(2,4-Dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl) acetamide

Produkt 1

HCID 10841112HCID 10841112, VerbindungAusbeute 59,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittel2×HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a stirring solution of 390 mg (0.86 mmol) of 2-(2,4-Dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl) acetamide, prepared as in Intermediate 4, in 10 mL of DMF at 0° C. is added 1.03 mL (1.03 mmol, 1.2 equiv) of a 1.0M solution of NaN(TMS)2 in THF. The resulting solution is stirred 5 min, and a solution of 200 mg (0.94 mmol, 1.1 equiv.) of 3-bromomethyl benzo[d]isoxazole (Uno, H.; Kurokawa, M.; Natsuka, K.; Yamato, Y.; Nishimura, H. Chem. Pharm. Bull. 1976, 24, 632)in 1 mL of DMF is added. The resulting solution is stirred for 14 h at RT then quenched with 5 mL of H2O. The reaction mixture is poured into 50 mL of Et2O and extracted with H2O (2×50 mL). The organic layer is separated, dried (MgSO4), and the solvents removed in vacuo. Purification by silica gel flash column chromatography using hexane/EtOAc 2/1 as eluent followed by lyophilization in acetonitrile/H2O afforded 303 mg of the title compound as a white amorphous solid: 1H NMR (CDCl3, 300 MHz) δ7.81 (d, 1H, J=7.8), 7.55-7.10 (m, 14H), 6.97 (m, 2H), 5.01 (m, 1H), 4.28 (m, 3H), 3.85 (m, 4H), 3.58 (dd, 1H, J=5.1, 16.6), 1.07 (d, 6H, J=6.6); low resolution MS (FAB)m/e 589 (MH+), 588 (M+), 424, 396; Anal. (C35H32N4O5) Calcd. C, 71.41; H, 5.48; N, 9.52 Found C, 71.48; H, 5.49; N, 9.47.

Aufarbeitung

  1. stirringThe resulting solution is stirred for 14 h at RT
  2. customthen quenched with 5 mL of H2O
  3. additionThe reaction mixture is poured into 50 mL of Et2O
  4. extractionextracted with H2O (2×50 mL)
  5. customThe organic layer is separated
  6. dry with materialdried (MgSO4)
  7. customthe solvents removed in vacuo
  8. customPurification by silica gel flash column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-30442cbe9e814c22a9edbc17b6fafef7
Quelldatensatz
uspto-grants-1999_01
Patentnummer
US05859007

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