3-(Chloromethyl)-5-phenyl-1,2,4-oxadiazole → HCID 67697062, compound

HRID 343109Notes

Reaction equation

HRID 343109 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])[CH2:3]1.Cl[CH2:34][C:35]1[N:39]=[C:38]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[O:37][N:36]=1>CN(C=O)C.C1(C)C=CC=CC=1>[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[CH2:34][C:35]1[N:39]=[C:38]([C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)[O:37][N:36]=1

Participants

5

Reactant 2

HCID 3021543-(Chloromethyl)-5-phenyl-1,2,4-oxadiazoleHCID 108124012-(2,4-Dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-phenyl acetamide

Product 1

HCID 67697062HCID 67697062, compoundYield 42.1%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirring solution of 200 mg (0.47 mmol) of 2-(2,4-Dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-phenyl acetamide in 4 mL DMF at 0° C. is added dropwise 0.98 mL (0.49 mmol, 1.05 equiv) of a 0.5N solution of KN(TMS)2 in toluene. The resulting solution is stirred 5 min, then 100 mg (0.51 mmol, 1.1 equiv) of 3-chloromethyl-5-phenyl-[1,2,4]oxadiazole is added. The reaction mixture is stirred 30 min at 0° C. then 14 h at RT. The reaction mixture is quenched with 1 mL of H2O and the solvent removed in vacuo. The residue is dissolved in 40 mL EtOAc, washed with 40 mL H2O, and the organic layer is dried (MgSO4) and the solvent removed in vacuo. The resulting oil is purified by silica gel flash column chromatography using hexane/EtOAc 2/1 as eluent followed by further purification via reverse phase MPLC using a C-18 column and 60% acetonitrile/40% H2O with 0.1% TFA as eluent followed by lyophilization to afford 116 mg of 2-[2,4-Dioxo-5-phenyl-3-(5-phenyl-[1,2,4]oxadiazol-3-ylmethyl)-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-phenyl acetamide as a white amorphous solid: 1H NMR (CDCl3, 300 MHz) δ8.07 (d, 2H, J=6.9), 7.59-7.13 (m, 16H), 7.00 (dd, 1H, J=1.3, 8.1), 5.01 (m, 1H), 4.27 (s, br, 2H), 4.1 (t, 1H, J=6.1), 3.66 (dd, 1H, J=7.8, 17.1), 3.50 (dd, 1H, J=6.1, 17.1) 1.08 (t, 6H, J=6.9); low resolution MS (FAB) m/e 586 (MH+), 451, 277, 227, 195.

Workup

  1. stirringThe reaction mixture is stirred 30 min at 0° C.
  2. custom14 h
  3. customat RT
  4. customThe reaction mixture is quenched with 1 mL of H2O
  5. customthe solvent removed in vacuo
  6. dissolutionThe residue is dissolved in 40 mL EtOAc
  7. washwashed with 40 mL H2O
  8. dry with materialthe organic layer is dried (MgSO4)
  9. customthe solvent removed in vacuo
  10. customThe resulting oil is purified by silica gel flash column chromatography
  11. customfollowed by further purification via reverse phase MPLC

Sources & evidence

ORD record
ord-c8764d4942164f78860083723b552a2e
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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