Methyl iodide → N-Isopropyl-N-(4-methoxy-phenyl)-2-(3-methyl-3-naphthalen-2-ylmethyl-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl) acetamide

HRID 343213Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 343213
[CH:1]([N:4]([C:38]1[CH:43]=[CH:42][C:41]([O:44][CH3:45])=[CH:40][CH:39]=1)[C:5](=[O:37])[CH2:6][N:7]1[C:13](=[O:14])[CH:12]([CH2:15][C:16]2[CH:25]=[CH:24][C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH:17]=2)[C:11](=[O:26])[N:10]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:9]2[CH:33]=[CH:34][CH:35]=[CH:36][C:8]1=2)([CH3:3])[CH3:2].[CH3:46][Si]([N-][Si](C)(C)C)(C)C.[Na+].CI>CN(C=O)C.C1COCC1>[CH:1]([N:4]([C:38]1[CH:43]=[CH:42][C:41]([O:44][CH3:45])=[CH:40][CH:39]=1)[C:5](=[O:37])[CH2:6][N:7]1[C:13](=[O:14])[C:12]([CH3:46])([CH2:15][C:16]2[CH:25]=[CH:24][C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH:17]=2)[C:11](=[O:26])[N:10]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:9]2[CH:33]=[CH:34][CH:35]=[CH:36][C:8]1=2)([CH3:2])[CH3:3]

Komponenten

6

Edukt 3

HCID 6328Methyl iodideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 67699115N-Isopropyl-N-(4-methoxy-phenyl)-2-(3-naphthalen-2-ylmethyl-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl) acetamide

Produkt 1

HCID 86753602N-Isopropyl-N-(4-methoxy-phenyl)-2-(3-methyl-3-naphthalen-2-ylmethyl-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl) acetamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

To a stirring solution of 200 mg (0.34 mmol) of N-Isopropyl-N-(4-methoxy-phenyl)-2-(3-naphthalen-2-ylmethyl-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl) acetamide, prepared as in Example 36, in 5 mL of DMF at 0° C. is added 0.60 mL (0.60 mmol, 1.8 equiv) of a 1.0M solution of NaN(TMS)2 in THF. The resulting solution is stirred 5 min, and 37 μL (0.60 mmol, 1.8 equiv) of methyl iodide is added. The resulting solution is stirred 3 h at RT, warmed to 50° C. for 16 h, and 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 of the material by silica gel MPLC on an Si60 column using hexane/EtOAc 5/2 as eluent followed by lyophilization in acetonitrile/H2O afforded 180 mg of the title compound as a white amorphous solid: 1H NMR (DMSO-d6, 300 MHz) δ7.88-7.79 (m, 3H), 7.64-7.19 (m, 14H), 7.05 (m, 2H), 6.92 (dd, 1H, J=1.0, 8.1), 4.87 (m, 1H), 4.30 (s, br, 2H), 3.80 (s, 3H), 2.76 (dd, 2H, J=13.9, 23.9), 1.22 (s, 3H), 1.00 (m, 6H); low resolution MS (FAB)m/e 612 (MH+), 611 (M+), 447.

Aufarbeitung

  1. stirringThe resulting solution is stirred 3 h at RT
  2. customquenched 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 of the material by silica gel MPLC on an Si60 column

Quellen und Nachweise

ORD-Eintrag
ord-f74b3468f42f438ab86a9ef929707ee7
Quelldatensatz
uspto-grants-1999_01
Patentnummer
US05859007

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