Cesium carbonate → methyl (4S,7S)-4-(5-(4-(6-bromoquinoxalin-2-yl)phenyl)-1H-imidazol-2-yl)-6,10-dioxooctahydro-1H-pyridazino[1,2-a][1,2]diazepin-7-ylcarbamate

HRID 709375Notes

Reaction equation

HRID 709375 reaction equation
[O:1]=[C:2]1[C@@H:8]([NH:9][C:10](=[O:13])[O:11][CH3:12])[CH2:7][CH2:6][C:5](=[O:14])[N:4]2[CH2:15][CH2:16][CH2:17][C@@H:18]([C:19]3[NH:20][C:21]([C:24]4[CH:29]=[CH:28][C:27](B5OC(C)(C)C(C)(C)O5)=[CH:26][CH:25]=4)=[CH:22][N:23]=3)[N:3]12.[Br:39][C:40]1[CH:41]=[C:42]2[C:47](=[CH:48][CH:49]=1)[N:46]=[C:45](Cl)[CH:44]=[N:43]2.C([O-])([O-])=O.[Cs+].[Cs+].O1CCOCC1>CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[Br:39][C:40]1[CH:41]=[C:42]2[C:47](=[CH:48][CH:49]=1)[N:46]=[C:45]([C:27]1[CH:26]=[CH:25][C:24]([C:21]3[NH:20][C:19]([C@H:18]4[N:3]5[C:2](=[O:1])[C@@H:8]([NH:9][C:10](=[O:13])[O:11][CH3:12])[CH2:7][CH2:6][C:5](=[O:14])[N:4]5[CH2:15][CH2:16][CH2:17]4)=[N:23][CH:22]=3)=[CH:29][CH:28]=1)[CH:44]=[N:43]2

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 126864086-Bromo-2-chloroquinoxalineHCID 90397526methyl (4S,7S)-6,10-dioxo-4-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-yl)octahydro-1H-pyridazino[1,2-a][1,2]diazepin-7-ylcarbamate2×

Product 1

HCID 131733895methyl (4S,7S)-4-(5-(4-(6-bromoquinoxalin-2-yl)phenyl)-1H-imidazol-2-yl)-6,10-dioxooctahydro-1H-pyridazino[1,2-a][1,2]diazepin-7-ylcarbamateYield 86.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

In a 10 ml seal tube, methyl (4S,7S)-6,10-dioxo-4-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-yl)octahydro-1H-pyridazino[1,2-a][1,2]diazepin-7-ylcarbamate (240 mg, 459 μmol) (Intermediate 3), 6-bromo-2-chloroquinoxaline (112 mg, 459 μmol) and Cs2CO3 (299 mg, 917 μmol) were combined with 1,4-dioxane (3.00 ml) and water (0.5 ml) to give a light brown solution. It was degassed for 10 min and tetrakis(triphenylphosphine)palladium (0) (53.0 mg, 45.9 μmol) was added. The reaction mixture was heated at 80° C. for 16 h. It was diluted with EtOAc (6 ml) and concentrated in vacuo. The residue was purified on a silica gel column (CH2Cl2, 2%, 3%, 5%, 8% and 10% MeOH/CH2Cl2) to afford methyl (4S,7S)-4-(5-(4-(6-bromoquinoxalin-2-yl)phenyl)-1H-imidazol-2-yl)-6,10-dioxooctahydro-1H-pyridazino[1,2-a][1,2]diazepin-7-ylcarbamate as a red solid (240 mg, 86.6%). ESI-LRMS m/e calcd for C28H26BrN7O4 [M+] 604. found 605 [M+H+].

Workup

  1. customIn a 10 ml seal tube
  2. customto give a light brown solution
  3. customIt was degassed for 10 min
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified on a silica gel column (CH2Cl2, 2%, 3%, 5%, 8% and 10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-b8a57c50edac41d48a6d0de5d292e398
Source dataset
uspto-grants-2015_11
Patent number
US09180193B2

Reaction notes

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