Dimethylformamide → HCID 10793168, compound

HRID 343202Notes

Reaction equation

HRID 343202 reaction equation
C(OC([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([CH2:17][CH:18]2[C:24](=[O:25])[N:23]([CH2:26][C:27]([N:29]([CH:36]([CH3:38])[CH3:37])[C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[O:28])[C:22]3C=[CH:40][CH:41]=[CH:42][C:21]=3N(C3C=CC=CC=3)[C:19]2=O)=[CH:9]1)=O)(C)(C)C.[H-].[Na+].CI.[CH3:54][N:55]([CH:57]=[O:58])[CH3:56]>>[NH:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([CH2:17][C:18]2([CH3:19])[C:24](=[O:25])[N:23]([CH2:26][C:27]([N:29]([CH:36]([CH3:38])[CH3:37])[C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)=[O:28])[C:22]3[CH:21]=[CH:42][CH:41]=[CH:40][C:54]=3[N:55]([C:56]3[CH:18]=[CH:17][CH:10]=[CH:11][CH:12]=3)[C:57]2=[O:58])=[CH:9]1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 86753601HCID 86753601, compound

Product 1

HCID 10793168HCID 10793168, compound

Conditions

Temperature
50 °C

Procedure

To a stirring solution of 210 mg (0.32 mmol) of 2-[3-(N-tert-butoxycarbonyl-indol-3-ylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-phenyl acetamide, prepared as in Intermediate 38, in 4 mL of DMF at 0° C. is added 19 mg (0.48 mmol, 1.5 equiv) of sodium hydride (60% dispersion in mineral oil). The resulting solution is stirred 5 min, then 30 mL (0.48 mmol, 1.5 equiv) of methyl iodide is added. The reaction mixture is stirred 2 h at RT and then heated to 50° C. for 14 h, then 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. The crude material is then dissolved in 2 mL of dichloromethane, 2 mL of TFA is added, and the reaction mixture is stirred 1 h at RT. The volatiles are removed in vacuo and the resulting crude oil purified via MPLC using a Si60 silica gel column and hexane/EtOAc 5/2 as eluent followed by lyophilization afforded 37 mg of the title compound as a white amorphous solid: 1H NMR (CDCl3, 300 MHz) δ8.11 (s, 1H), 7.61-7.00 (m, 18H), 6.76 (d, 1H, J=5.1), 5.10 (m, 1H), 4.50 (d, 1H, J=16.4), 3.95 (d, 1H, J=16.4), 2.91 (dd, 2H), 1.58 (s, 3H), 1.14 (m, 6H); low resolution MS (FAB)m/e 571 (MH+).

Workup

  1. stirringThe reaction mixture is stirred 2 h at RT
  2. customquenched 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. dissolutionThe crude material is then dissolved in 2 mL of dichloromethane
  8. addition2 mL of TFA is added
  9. stirringthe reaction mixture is stirred 1 h at RT
  10. customThe volatiles are removed in vacuo
  11. customthe resulting crude oil purified via MPLC

Sources & evidence

ORD record
ord-c5a7b28e47314f919a82793769f8b4bd
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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