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

温度

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レコード

ord-4f9b9bd541754dc0b0d52bce31e61f60

出典データセット

uspto-grants-1999_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US05859007