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

HRID 343214Notes

Reaction equation

HRID 343214 reaction equation
[S:1]1[CH:5]=[C:4]([CH2:6][CH:7]2[C:13](=[O:14])[N:12]([CH2:15][C:16]([N:18]([CH:27]([CH3:29])[CH3:28])[C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)=[O:17])[C:11]3[CH:30]=[CH:31][CH:32]=[CH:33][C:10]=3[N:9]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[C:8]2=[O:40])[C:3]2[CH:41]=[CH:42][CH:43]=[CH:44][C:2]1=2.[CH3:45][Si]([N-][Si](C)(C)C)(C)C.[Na+].CI>CN(C=O)C.C1COCC1>[S:1]1[CH:5]=[C:4]([CH2:6][C:7]2([CH3:45])[C:13](=[O:14])[N:12]([CH2:15][C:16]([N:18]([CH:27]([CH3:29])[CH3:28])[C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)=[O:17])[C:11]3[CH:30]=[CH:31][CH:32]=[CH:33][C:10]=3[N:9]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[C:8]2=[O:40])[C:3]2[CH:41]=[CH:42][CH:43]=[CH:44][C:2]1=2

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 106036912-(3-Benzo[b]thiophen-3-ylmethyl-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl) acetamide

Product 1

HCID 676967932-(3-Benzo[b]thiophen-3-ylmethyl-3-methyl-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl) acetamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a stirring solution of 130 mg (0.22 mmol) of 2-(3-Benzo[b]thiophen-3-ylmethyl-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 Example 37, in 5 mL of DMF at 0° C. is added 0.43 mL (0.43 mmol, 2.0 equiv) of a 1.0M solution of NaN(TMS)2 in THF. The resulting solution is stirred 5 min, and 27 μL (0.43 mmol, 2.0 equiv) of methyl iodide is added. The resulting solution is stirred 4 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 3/1 as eluent followed by lyophilization in acetonitrile/H2O afforded 106 mg of the title compound as a white amorphous solid: 1H NMR (DMSO-d6, 300 MHz) δ7.92 (m, 1H), 7.66-7.05 (m, 16H), 6.81 (d, 1H, J=8.1), 4.85 (m, 1H), 4.31 (s, br, 2H), 3.80 (s, 3H), 2.97 (d, 1H, J=15.2), 2.77 (d, 1H, J=15.2), 1.20 (s, 3H), 1.00 (m, 6H); low resolution MS (FAB)m/e 618 (MH+), 617 (M+), 453; Anal. (C37H35N3O4S) Calcd. C, 71.71; H, 5.74; N, 6.76; S, 5.26 Found C, 71.94; H, 5.71; N, 6.80; S, 5.19.

Workup

  1. stirringThe resulting solution is stirred 4 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

Sources & evidence

ORD record
ord-c12eb515082745f6984a8cd969c61236
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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