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

HRID 48337Notes

Reaction equation

HRID 48337 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:27]=[CH:26][CH:25]=[C:24]([O:28][CH3:29])[CH:23]=3)[CH:20]=[CH:21][C:11]1=2)(=O)OCC)C.[H-].[Na+].[Cl:32][C:33]1[CH:38]=[CH:37][C:36]([S:39][C:40]2[CH:47]=[CH:46][CH:45]=[CH:44][C:41]=2[CH:42]=O)=[CH:35][CH:34]=1>O1CCCC1>[ClH:32].[ClH:32].[Cl:32][C:33]1[CH:38]=[CH:37][C:36]([S:39][C:40]2[CH:47]=[CH:46][CH:45]=[CH:44][C:41]=2[CH:42]=[CH:9][C:10]2=[N:16][CH2:15][CH2:14][N:13]([CH3:17])[C:12]3[CH:18]=[C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH3:29])[CH:23]=4)[CH:20]=[CH:21][C:11]2=3)=[CH:35][CH:34]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27786242-(4-Chlorophenylthio)BenzaldehydeHCID 86585814[8-(3-Methoxyphenyl)-1-methyl-1,2,3,4-tetrahydrobenzo[e][1,4]diazepin-5-ylidenemethyl]phosphonic acid diethyl ester

Product 1

HCID 69892946(E)-5-[2-(4-chlorophenylthio)styryl]-2,3-dihydro-8-(3-methoxyphenyl)-1-methyl-1H-1,4-benzodiazepine dihydrochlorideYield 18.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To 112 mg (0.27 mmol) of [8-(3-methoxyphenyl)-1-methyl-1,2,3,4-tetrahydro-benzo[e][1,4]diazepin-5-ylidenemethyl]phosphonic acid diethyl ester (prepared as described in Example 98) in 2 ml of tetrahydrofuran was added 19 mg (0.47 mmol) of sodium hydride (60% dispersion in mineral oil). After 10 minutes 70 mg (0.28 mmol) of 2-(4-chlorophenylthio)benzaldehyde 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/ethyl acetate and treated with 0.10 ml of 4M hydrogen chloride in dioxan. The solvent was evaporated to leave an orange gum which was recrystallized from ethyl acetate to give 10 mg of (E)-5-[2-(4-chlorophenylthio)styryl]-2,3-dihydro-8-(3-methoxyphenyl)-1-methyl-1H-1,4-benzodiazepine dihydrochloride as a red solid; MS: m/e 510 (M+).

Workup

  1. customThe product was purified by column chromatography (20 g IST pre-packed column)
  2. washeluting with 1% methanol/ethyl acetate
  3. additiontreated with 0.10 ml of 4M hydrogen chloride in dioxan
  4. customThe solvent was evaporated
  5. customto leave an orange gum which
  6. customwas recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-55ed4c970e554c55b2c8200809bab998
Source dataset
uspto-grants-2004_03
Patent number
US06703387B2

Reaction notes

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