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

HRID 48338

Reaction equation

HRID 48338 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]([C:22]3[CH:26]=[CH:25][S:24][CH:23]=3)[CH:20]=[CH:21][C:11]1=2)(=O)OCC)C.[H-].[Na+].[Cl:29][C:30]1[CH:31]=[C:32]([CH:35]=[CH:36][C:37]=1[Cl:38])[CH:33]=O>O1CCCC1>[ClH:29].[ClH:29].[Cl:29][C:30]1[CH:31]=[C:32]([CH:35]=[CH:36][C:37]=1[Cl:38])[CH:33]=[CH:9][C:10]1=[N:16][CH2:15][CH2:14][N:13]([CH3:17])[C:12]2[CH:18]=[C:19]([C:22]3[CH:26]=[CH:25][S:24][CH:23]=3)[CH:20]=[CH:21][C:11]1=2

Participants

5

Reactant 3

HCID 227103,4-DichlorobenzaldehydeHCID 24758Sodium hydrideHCID 86585816(1-Methyl-8-thiophen-3-yl-1,2,3,4-tetrahydrobenzo [e][1,4]diazepin-5-ylidenemethyl)phosphonic acid diethyl ester

Product 1

HCID 69893578(E)-5-(3,4-dichlorostyryl)-2,3-dihydro-1-methyl-8-(3-thienyl)-1H-1,4-benzodiazepine dihydrochlorideYield 165.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To 105 mg (0.27 mmol) of (1-methyl-8-thiophen-3-yl-1,2,3,4-tetrahydrobenzo[e][1,4]diazepin-5-ylidenemethyl)phosphonic acid diethyl ester in 2 ml of tetrahydrofuran was added 19 mg (0.47 mmol) of sodium hydride (60% dispersion in mineral oil). After 10 minutes 49 mg (0.28 mmol) of 3,4-dichlorobenzaldehyde was added and the mixture was stirred for 3 hours. The product was purified by column chromatography (20 g IST pre-packed column) eluting with 1% methanol/dichloromethane and treated with 0.15 ml of 4M hydrogen chloride in dioxan. The solvent was evaporated and the residue was recrystallized from acetone to give 75 mg of (E)-5-(3,4-dichlorostyryl)-2,3-dihydro-1-methyl-8-(3-thienyl)-1H-1,4-benzodiazepine dihydrochloride as an orange solid; MS: 412 (M+).

Workup

  1. customThe product was purified by column chromatography (20 g IST pre-packed column)
  2. washeluting with 1% methanol/dichloromethane
  3. additiontreated with 0.15 ml of 4M hydrogen chloride in dioxan
  4. customThe solvent was evaporated
  5. customthe residue was recrystallized from acetone

Sources & evidence

ORD record
ord-e6b4d448a4774602ba6420691c38eed0
Source dataset
uspto-grants-2004_03
Patent number
US06703387B2

Linked notes

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