3,4-Dichlorobenzaldehyde → (E)-5-(3,4-dichlorostyryl)-2,3-dihydro-1-methyl-8-vinyl-1H-1,4-benzodiazepine dihydrochloride

HRID 48340

Reaction equation

HRID 48340 reaction equation
C(OP([CH:9]=[C:10]1[NH:16][CH2:15][CH2:14][N:13]([CH3:17])[C:12]2[CH:18]=[C:19](Br)[CH:20]=[CH:21][C:11]1=2)(=O)OCC)C.[CH:23]([Sn](CCCC)(CCCC)CCCC)=[CH2:24].[H-].[Na+].[Cl:40][C:41]1[CH:42]=[C:43]([CH:46]=[CH:47][C:48]=1[Cl:49])[CH:44]=O>O1CCOCC1>[ClH:40].[ClH:40].[Cl:40][C:41]1[CH:42]=[C:43]([CH:46]=[CH:47][C:48]=1[Cl:49])[CH:44]=[CH:9][C:10]1=[N:16][CH2:15][CH2:14][N:13]([CH3:17])[C:12]2[CH:18]=[C:19]([CH:23]=[CH2:24])[CH:20]=[CH:21][C:11]1=2

Participants

6

Reactant 4

HCID 227103,4-DichlorobenzaldehydeHCID 24758Sodium hydrideHCID 81998TributylvinyltinHCID 86585809(8-Bromo-1-methyl-1,2,3,4-tetrahydrobenzo[e][1,4]diazepin-5-ylidenemethyl)phosphonic acid diethyl ester

Product 1

HCID 69893209(E)-5-(3,4-dichlorostyryl)-2,3-dihydro-1-methyl-8-vinyl-1H-1,4-benzodiazepine dihydrochlorideYield 52.8%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To 123 mg (0.32 mmol) of (8-bromo-1-methyl-1,2,3,4-tetrahydrobenzo[e][1,4]diazepin-5-ylidenemethyl)phosphonic acid diethyl ester (prepared as described in Example 41) in 2 ml of dioxane was added 120 mg (0.38 mmol) of vinyl tributylstannane, followed by 11.1 mg (0.016 mmol)of palladium (II) bis-triphenylphosphine-dichloride. The mixture was heated at 80° C. for 18 hours. To the mixture at ambient temperature was added 22 mg (0.55 mmol) of sodium hydride (60% dispersion in mineral oil). After 5 minutes 57 mg (0.33 mmol) of 3,4-dichlorobenzaldehyde was added and the mixture was stirred for 18 hours. The solvent was removed and the product was purified by column chromatography eluting with 1-4% methanol/dichloromethane and treated with 0.10 ml of 4M hydrogen chloride in dioxan. The solvent was evaporated and the residue was dissolved from acetone/petroleum ether (40 60° C.). The solvent was removed to give 25 mg of (E)-5-(3,4-dichlorostyryl)-2,3-dihydro-1-methyl-8-vinyl-1H-1,4-benzodiazepine dihydrochloride as a red solid; MS: 357 (M+).

Workup

  1. customThe solvent was removed
  2. customthe product was purified by column chromatography
  3. washeluting with 1-4% methanol/dichloromethane
  4. additiontreated with 0.10 ml of 4M hydrogen chloride in dioxan
  5. customThe solvent was evaporated
  6. dissolutionthe residue was dissolved from acetone/petroleum ether (40 60° C.)
  7. customThe solvent was removed

Sources & evidence

ORD record
ord-cc8d073d6c444914a43bb7c3be5c3a28
Source dataset
uspto-grants-2004_03
Patent number
US06703387B2

Linked notes

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