Dimethylformamide → HCID 57642316, compound

HRID 2112493Notes

Reaction equation

HRID 2112493 reaction equation
Br[C:2]1[C:3]([O:21][CH3:22])=[CH:4][C:5]2[NH:11][C:10](=[O:12])[CH2:9][N:8]=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:19])[C:6]=2[CH:20]=1.[CH3:23][N:24](C)C=O>[Pd].C(OCC)(=O)C.[C-]#N.[Zn+2].[C-]#N>[Cl:19][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[C:7]1[C:6]2[CH:20]=[C:2]([C:23]#[N:24])[C:3]([O:21][CH3:22])=[CH:4][C:5]=2[NH:11][C:10](=[O:12])[CH2:9][N:8]=1

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 57642322HCID 57642322, compound2×

Product 1

HCID 57642316HCID 57642316, compound

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)Catalyst2×HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

5-(2-chlorophenyl)-7-cyano-1,3-dihydro-8-methoxy-2H-1,4-benzodiazepin-2-one (Ib) was prepared from 7-bromo-5-(2-chlorophenyl)-1,3-dihydro-8-methoxy-2H-1,4-benzodiazepin-2-one (Id) by reaction with zinc cyanide in the presence of a palladium catalyst (tetrakistriphenyl phosphine palladium) according to conditions similar to those described by Tschaen et al., Synthetic Communications, 24:887-90 (1994). A mixture of 0.9491 g (0.0025 mole) of 7-bromo-5-(2-chlorophenyl)-1,3-dihydro-8-methoxy-2H-1,4-benzodiazepin-2-one (Id), 0.176 g (0.0015 mole) of zinc cyanide, 4 mL of dimethylformamide and 0.289 g (0.00025 mole) of tetrakistriphenyl phosphine palladium was heated at 110° C. under an argon atmosphere for 24 hours. The mixture was then cooled, taken up in ethyl acetate and washed with 0.2 M sodium carbonate solution. The aqueous phase was reextracted with ethyl acetate, and the ethyl acetate layers washed with water, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was chromatographed on silica gel eluting with ethyl acetate-hexane (4:1) to give 0.620 g of 5-(2-chlorophenyl)-7-cyano-1,3-dihydro-8-methoxy-2H-1,4-benzodiazepin-2-one (Ib). MH+/Z=326.

Workup

  1. temperatureThe mixture was then cooled
  2. washwashed with 0.2 M sodium carbonate solution
  3. washthe ethyl acetate layers washed with water
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was chromatographed on silica gel eluting with ethyl acetate-hexane (4:1)

Sources & evidence

ORD record
ord-cdee4e0cc83149f6be84cad17a164883
Source dataset
uspto-grants-2009_04
Patent number
US07524840B2

Reaction notes

Loading…