Sodium hydride → (E)-5-[2-(4-chlorophenylthio)styryl]-8-(2-furyl)-2,3-dihydro-1-methyl-1H-1,4-benzodiazepine dihydrochloride

HRID 48341Notes

Reaction equation

HRID 48341 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.C([Sn](CCCC)(CCCC)[C:28]1[O:29][CH:30]=[CH:31][CH:32]=1)CCC.[H-].[Na+].[Cl:43][C:44]1[CH:49]=[CH:48][C:47]([S:50][C:51]2[CH:58]=[CH:57][CH:56]=[CH:55][C:52]=2[CH:53]=O)=[CH:46][CH:45]=1>O1CCOCC1>[ClH:43].[ClH:43].[Cl:43][C:44]1[CH:45]=[CH:46][C:47]([S:50][C:51]2[CH:58]=[CH:57][CH:56]=[CH:55][C:52]=2[CH:53]=[CH:9][C:10]2=[N:16][CH2:15][CH2:14][N:13]([CH3:17])[C:12]3[CH:18]=[C:19]([C:30]4[O:29][CH:28]=[CH:32][CH:31]=4)[CH:20]=[CH:21][C:11]2=3)=[CH:48][CH:49]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 27786242-(4-Chlorophenylthio)BenzaldehydeHCID 43936882-(Tributylstannyl)furanHCID 86585809(8-Bromo-1-methyl-1,2,3,4-tetrahydrobenzo[e][1,4]diazepin-5-ylidenemethyl)phosphonic acid diethyl ester

Product 1

HCID 69893152(E)-5-[2-(4-chlorophenylthio)styryl]-8-(2-furyl)-2,3-dihydro-1-methyl-1H-1,4-benzodiazepine dihydrochlorideYield 105.3%

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 135 mg (0.38 mmol) of 2-(tributylstannyl)furan, 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 55 mg (1.37 mmol) of sodium hydride (60% dispersion in mineral oil). After 5 minutes 82 mg (0.33 mmol) of 2-(4-chlorophenylthio)benzaldehyde was added and the mixture was stirred for 18 hours. The solvent was removed and the product was purified by column chromatography eluting with 24-40% acetone/petroleum ether (40-60° C.) 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 and the residue was recrystallised from acetone/petroleum ether (40 60° C.) to give 63 mg of (E)-5-[2-(4-chlorophenylthio)styryl]-8-(2-furyl)-2,3-dihydro-1-methyl-1H-1,4-benzodiazepine dihydrochloride as dark red crystals; MS: m/e 471 (M+).

Workup

  1. customThe solvent was removed
  2. customthe product was purified by column chromatography
  3. washeluting with 24-40% acetone/petroleum ether (40-60° C.)
  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
  8. customthe residue was recrystallised from acetone/petroleum ether (40 60° C.)

Sources & evidence

ORD record
ord-4a80ecd0dfd14fc699043a64f4188fa7
Source dataset
uspto-grants-2004_03
Patent number
US06703387B2

Reaction notes

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