Dimethylformamide → HCID 86753599, compound

HRID 343201Notes

Reaction equation

HRID 343201 reaction equation
C(OC([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[C:9]1[CH2:17][CH:18]1[C:24](=[O:25])[N:23]([CH2:26][C:27]([N:29]([CH:36]([CH3:38])[CH3:37])[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[O:28])[C:22]2C=[CH:40][CH:41]=[CH:42][C:21]=2N(C2C=CC=CC=2)[C:19]1=O)=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)[CH:10]=[C:9]1[CH2:17][C:18]1([CH3:19])[C:24](=[O:25])[N:23]([CH2:26][C:27]([N:29]([CH:36]([CH3:38])[CH3:37])[C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)=[O:28])[C:22]2[CH:21]=[CH:42][CH:41]=[CH:40][C:54]=2[N:55]([C:56]2[CH:18]=[CH:17][CH:9]=[CH:10][CH:11]=2)[C:57]1=[O:58]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 86753600HCID 86753600, compound

Product 1

HCID 86753599HCID 86753599, compound

Conditions

Temperature
50 °C

Procedure

To a stirring solution of 190 mg (0.28 mmol) of 2-[3-(N-tert-butoxycarbonyl-indol-2-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 37, in 4 mL of DMF at 0° C. is added 17 mg (0.43 mmol, 1.5 equiv) of sodium hydride (60% dispersion in mineral oil). The resulting solution is stirred 5 min, then 26 μL (0.43 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 3 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 3 mL of dichloromethane, 1 mL of TFA is added, and the reaction mixture is stirred 3 h at RT. The volatiles are removed in vacuo and the resulting crude oil purified via reverse phase MPLC using a C-18 column and 75% acetonitrile/25% H2O with 0.1% TFA as eluent followed by lyophilization afforded 15 mg of the title compound as a white amorphous solid: 1H NMR (CDCl3, 300 MHz) δ9.22 (s, 0.33H), 7.68-7.00 (m, 17H), 6.84 (m, 1H), 6.28 (s, 0.33H), 6.16 (s, 0.66H), 5.26 (m, 0.66H), 5.10 (m, 0.33H), 4.72 (d, 0.66H, J=16.3), 4.45 (d, 0.33H, J=16.6), 4.02 (m, 0.33H), 3.82 (d, 0.66H, J=16.3), 3.70 (m, 0.33H), 3.45 (d, 0.33H), 3.15 (d, 0.66H, J=14.9), 2.62 (d, 0.66H, J=14.9), 1.42 (s, 2H), 1.26 (m, 7H); 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 3 mL of dichloromethane
  8. addition1 mL of TFA is added
  9. stirringthe reaction mixture is stirred 3 h at RT
  10. customThe volatiles are removed in vacuo
  11. customthe resulting crude oil purified via reverse phase MPLC

Sources & evidence

ORD record
ord-6e769b0e97af4d3081933fe211de7897
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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