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

HRID 343210Notes

Reaction equation

HRID 343210 reaction equation
[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[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]=[CH:18][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[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]=[CH:18][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]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 67699931N-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

Product 1

HCID 67699309N-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

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-4f9b9bd541754dc0b0d52bce31e61f60
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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