Lithium Chloride → HCID 70664468, compound

HRID 1186097Notes

Reaction equation

HRID 1186097 reaction equation
Cl[C:2]1[C:3]2[CH:31]=[C:30]([Cl:32])[CH:29]=[CH:28][C:4]=2[N:5]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)[C:6](=[O:18])[CH:7]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=2[Cl:17])[N:8]=1.[Cl-].[Li+].O.[OH-].[Cs+].[CH3:38][O:39][C:40]1[CH:45]=[CH:44][C:43](B2OC(C)(C)C(C)(C)O2)=[CH:42][C:41]=1[CH3:55]>O1CCOCC1.O.C(OCC)(=O)C>[Cl:32][C:30]1[CH:29]=[CH:28][C:4]2[N:5]([CH2:19][C:20]3[CH:21]=[CH:22][C:23]([O:26][CH3:27])=[CH:24][CH:25]=3)[C:6](=[O:18])[CH:7]([CH2:9][C:10]3[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=3[Cl:17])[N:8]=[C:2]([C:43]3[CH:44]=[CH:45][C:40]([O:39][CH3:38])=[C:41]([CH3:55])[CH:42]=3)[C:3]=2[CH:31]=1

Participants

8

Reactant 4

HCID 433294Lithium ChlorideHCID 21923912HCID 21923912, compoundHCID 23679066Caesium hydroxide--water (1/1/1)HCID 67060852HCID 67060852, compound

Product 1

HCID 70664468HCID 70664468, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
160 °C

Procedure

5,7-Dichloro-3-(2-chloro-4-fluorobenzyl)-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (0.3 g, 0.61 mmol) was combined with lithium chloride (0.078 g, 1.83 mmol), cesium hydroxide hydrate (0.31 g, 1.83 mmol) and 2-(4-methoxy-3-methylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.151 g, 0.61 mmol) in 1,4-dioxane (3 mL) and water (0.3 mL) and the mixture was purged with nitrogen. [Tetrakis(triphenylphosphine)]palladium(0) (0.07 g, 0.061 mmol) was added and the mixture was heated in a CEM Discover microwave reactor at 160° C. for 20 minutes. The mixture was allowed to cool and diluted with ethyl acetate then washed with water then brine. The organic layer was concentrated onto silica gel and chromatographed on a silica gel column eluting with 10-35% ethyl acetate in hexanes to give 7-chloro-3-(2-chloro-4-fluorobenzyl)-5-(4-methoxy-3-methylphenyl)-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one.

Workup

  1. customthe mixture was purged with nitrogen
  2. temperatureto cool
  3. washthen washed with water
  4. concentrationThe organic layer was concentrated onto silica gel
  5. customchromatographed on a silica gel column
  6. washeluting with 10-35% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-e8138bf435274d53a0214dae79825e33
Source dataset
uspto-grants-2014_03
Patent number
US08673897B2

Reaction notes

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