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

HRID 343197Notes

Reaction equation

HRID 343197 reaction equation
[O:1]=[C:2]1[N:8]([CH2:9][C:10]([N:12]([CH:19]([CH3:21])[CH3:20])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:11])[C:7]2[CH:22]=[CH:23][CH:24]=[CH:25][C:6]=2[N:5]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:4](=[O:32])[CH:3]1[CH2:33][CH:34]=[CH:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.[H-].[Na+].[CH3:44]I>CN(C=O)C>[CH:19]([N:12]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:10](=[O:11])[CH2:9][N:8]1[C:2](=[O:1])[C:3]([CH3:44])([CH2:33][CH:34]=[CH:35][C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)[C:4](=[O:32])[N:5]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:6]2[CH:25]=[CH:24][CH:23]=[CH:22][C:7]1=2)([CH3:21])[CH3:20]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 676981572-[2,4-Dioxo-5-phenyl-3-(3-phenyl-allyl)-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-phenyl acetamide

Product 1

HCID 67699497N-Isopropyl-2-[3-methyl-2,4-dioxo-5-phenyl-3-(3-phenyl-allyl)-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-phenyl acetamideYield 51.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirring solution of 200 mg (0.37 mmol) of 2-[2,4-Dioxo-5-phenyl-3-(3-phenyl-allyl)-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-phenyl acetamide, prepared as in Intermediate 41, in 3 mL of DMF at 0° C. is added 16 mg (0.41 mmol, 1.1 equiv) of sodium hydride (60% dispersion in mineral oil). The resulting solution is stirred 5 min, then 25 mL (0.41 mmol, 1.1 equiv) of methyl iodide is added. The reaction mixture is stirred 30 min at 0° C. then 19 h at RT and quenched with 1 mL H2O. The reaction mixture is diluted with 40 mL EtOAc and washed with 40 mL H2O. The organic layer is dried (MgSO4) and the solvents removed in vacuo. Purification of the resulting oil via reverse phase MPLC using a C-18 column and 70% acetonitrile/30% H2O with 0.1% TFA as eluent followed by lyophilization afforded 107 mg of the title compound as a white amorphous solid: 1H NMR (CDCl3, 300 MHz) δ7.53-7.05 (m, 18H), 6.79 (m, 1H), 6.15 (m, 1H), 5.97 (d, 1H, J=15.7), 5.09 (m, 1H), 4.44 (d, 1H, J=16.4), 3.95 (d, 1H, J=16.4), 3.07 (m, 2H), 2.28 (d, 1H, J=7.1), 1.61 (s, 3H), 1.14 (m, 6H); low resolution MS (FAB)m/e 558 (MH+), 423, 223.

Workup

  1. stirringThe reaction mixture is stirred 30 min at 0° C.
  2. custom19 h at RT and quenched with 1 mL H2O
  3. additionThe reaction mixture is diluted with 40 mL EtOAc
  4. washwashed with 40 mL H2O
  5. dry with materialThe organic layer is dried (MgSO4)
  6. customthe solvents removed in vacuo
  7. customPurification of the resulting oil via reverse phase MPLC

Sources & evidence

ORD record
ord-c6afec80751c416aa61e6fe43f346f50
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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