1,4-Dioxane → benzyl (4S,7S)-4-(5-(4-bromophenyl)-1H-imidazol-2-yl)-6,10-dioxooctahydro-1H-pyridazino[1,2-a][1,2]diazepin-7-ylcarbamate

HRID 709374Notes

Reaction equation

HRID 709374 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH2:9][NH:10][C:11]([C@H:13]2[N:18]3[C:19](=[O:36])[C@@H:20]([NH:25][C:26](=[O:35])[O:27][CH2:28][C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[CH2:21][CH2:22][C:23](=[O:24])[N:17]3[CH2:16][CH2:15][CH2:14]2)=O)=[CH:4][CH:3]=1.O1CCOCC1.C([O-])(=O)C.[NH4+:48]>CCOC(C)=O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[NH:48][C:11]([C@H:13]3[N:18]4[C:19](=[O:36])[C@@H:20]([NH:25][C:26](=[O:35])[O:27][CH2:28][C:29]5[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=5)[CH2:21][CH2:22][C:23](=[O:24])[N:17]4[CH2:16][CH2:15][CH2:14]3)=[N:10][CH:9]=2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 312751,4-DioxaneHCID 517165Ammonium AcetateHCID 131733894benzyl (4S,7S)-4-(2-(4-bromophenyl)-2-oxoethylcarbamoyl)-6,10-dioxooctahydro-1H-pyridazino[1,2-a][1,2]diazepin-7-ylcarbamate

Product 1

HCID 89510323benzyl (4S,7S)-4-(5-(4-bromophenyl)-1H-imidazol-2-yl)-6,10-dioxooctahydro-1H-pyridazino[1,2-a][1,2]diazepin-7-ylcarbamateYield 34.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

In a 10 ml, seal tube, benzyl (4S,7S)-4-(2-(4-bromophenyl)-2-oxoethylcarbamoyl)-6,10-dioxooctahydro-1H-pyridazino[1,2-a][1,2]diazepin-7-ylcarbamate (200 mg, 350 μmol) was combined with 1,4-dioxane (5 ml) to give a light yellow solution. Ammonium acetate (270 mg, 3.5 mmol) was added and the reaction mixture was heated at 110° C. for 12 hr. It was cooled and diluted with EtOAc (2×30 ml). The combined organic layers were washed with brine and H2O, dried with MgSO4 and concentrated in vacuo to afford a viscous oil. The crude was purified on a silica gel column (CH2Cl2, 2%, 4%, 6%, 8% MeOH/CH2Cl2) to afford benzyl (4S,7S)-4-(5-(4-bromophenyl)-1H-imidazol-2-yl)-6,10-dioxooctahydro-1H-pyridazino[1,2-a][1,2]diazepin-7-ylcarbamate as a yellow solid (66 mg, 34.1%). ESI-LRMS m/e calcd for C26H26BrN5O4 [M+] 552. found 553 [M+H+].

Workup

  1. customIn a 10 ml, seal tube
  2. customto give a light yellow solution
  3. temperatureIt was cooled
  4. washThe combined organic layers were washed with brine and H2O
  5. dry with materialdried with MgSO4
  6. concentrationconcentrated in vacuo
  7. customto afford a viscous oil
  8. customThe crude was purified on a silica gel column (CH2Cl2, 2%, 4%, 6%, 8% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-1c7f8c584c944adaa429b3b9631b55b5
Source dataset
uspto-grants-2015_11
Patent number
US09180193B2

Reaction notes

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