Sodium Iodide → 1-methyl-2-[1-(S)-methoxycarbonyl-2-phenylethylamino]methyl-5-(2'-fluorophenyl)-2,3-dihydro-1H-1,4-benzodiazepine

HRID 1591257

Reaction equation

HRID 1591257 reaction equation
[CH3:1][N:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[C:6]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[F:19])=[N:5][CH2:4][CH:3]1[CH2:20]Cl.[CH3:22][O:23][C:24](=[O:34])[C@@H:25]([NH2:33])[CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[Na+]>CN(C)C=O>[CH3:1][N:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[C:6]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[F:19])=[N:5][CH2:4][CH:3]1[CH2:20][NH:33][C@H:25]([C:24]([O:23][CH3:22])=[O:34])[CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 736234L-Phenylalanine, methyl esterHCID 134856441-methyl-2-chloromethyl-5-(2'-fluorophenyl)-2,3-dihydro-1H-1,4-benzodiazepine

Product 1

HCID 186115641-methyl-2-[1-(S)-methoxycarbonyl-2-phenylethylamino]methyl-5-(2'-fluorophenyl)-2,3-dihydro-1H-1,4-benzodiazepine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

1-Methyl-2-chloromethyl-5-(2'-fluorophenyl)-2,3-dihydro-1H-1,4-benzodiazepine (150 mg, 0.5 mmole) and methyl-2(S)-amino-3-phenylpropionate (108 mg, 0.5 mmole) were combined in 4 ml of dry N,N-dimethylformamide, and potassium carbonate (138 mg, 1 mmole) and sodium iodide (70 mg, 0.5 mmole) were added to this mixture. The reaction mixture was protected from moisture and heated at 60° C. for 48 hours. The solvent was then removed under reduced pressure and the residue was partitioned between ethyl acetate (100 ml) and saturated sodium bicarbonate solution (50 ml). The phases were separated and the organic layer was washed with sodium bicarbonate solution and brine, then dried (MgSO4) and concentrated to yield 300 mg of crude product. The analytical product was obtained via chromatography on silica gel (ethyl acetate-hexane elution, 7:3 v/v) as a mixture of diasteriomers; 95% pure by HPLC.

Workup

  1. customThe solvent was then removed under reduced pressure
  2. customthe residue was partitioned between ethyl acetate (100 ml) and saturated sodium bicarbonate solution (50 ml)
  3. customThe phases were separated
  4. washthe organic layer was washed with sodium bicarbonate solution and brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customto yield 300 mg of crude product
  8. customThe analytical product was obtained via chromatography on silica gel (ethyl acetate-hexane elution, 7:3 v/v) as a mixture of diasteriomers

Sources & evidence

ORD record
ord-699fa4b18c464ab78805eac6dab83587
Source dataset
uspto-grants-1993_04
Patent number
US05206238

Linked notes

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