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

Temperatur

50 °C

To a stirring solution of 150 mg (0.25 mmol) of N-Isopropyl-N-(4-methoxy-phenyl)-2-(3-naphthalen-1-ylmethyl-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl) acetamide, prepared as in Example 34, in 5 mL of DMF at 0° C. is added 0.45 mL (0.45 mmol, 1.8 equiv) of a 1.0M solution of NaN(TMS)2 in THF. The resulting solution is stirred 5 min, and 28 μL (0.45 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 then 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 3/1 as eluent followed by lyophilization in acetonitrile/H2O afforded 120 mg of the title compound as a white amorphous solid: 1H NMR (DMSO-d6, 300 MHz) δ7.93-7.86 (m, 2H), 7.77 (d, 1H, J=8.0), 7.60-7.06 (m, 16H), 6.89 (dd, 1H, J=0.8, 8.1), 4.88 (m, 1H), 4.34 (s, br, 2H), 3.81 (s, 3H), 3.20 (d, 1H, J=14.7), 3.00 (d, 1H, J=14.7), 1.01 (m, 9H); low resolution MS (FAB)m/e 612 (MH+), 611 (M+), 447.

1. stirringThe resulting solution is stirred 3 h at RT
2. customquenched with 5 mL of H2O
3. additionThe reaction mixture is then 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

ORD-Eintrag

ord-4f9b9bd541754dc0b0d52bce31e61f60

Quelldatensatz

uspto-grants-1999_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05859007