Bromazepam → 7-Bromo-1,3-dihydro-5-(2-pyridyl)-2H-1,4-benzodiazepin-2-ylidenepropanedioic acid diethyl ester

HRID 1156236Notes

Reaction equation

HRID 1156236 reaction equation
C([C:3]([CH2:10][CH3:11])([C:7]([O-:9])=[O:8])[C:4]([O-:6])=[O:5])C.[H-].[Na+].P(Cl)(OCC)(O[CH2:17][CH3:18])=O.[Br:23][C:24]1[CH:25]=[CH:26][C:27]2[NH:33]C(=O)C[N:30]=[C:29]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=3)[C:28]=2[CH:41]=1.[CH2:42]1COC[CH2:43]1>>[CH2:17]([O:9][C:7](=[O:8])[C:3](=[C:10]1[CH2:11][N:30]=[C:29]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=2)[C:28]2[CH:41]=[C:24]([Br:23])[CH:25]=[CH:26][C:27]=2[NH:33]1)[C:4]([O:6][CH2:42][CH3:43])=[O:5])[CH3:18]

Participants

6

Reactant 5

HCID 2441BromazepamHCID 8028Tetrahydrofuran2×HCID 13139Diethyl chlorophosphateHCID 24758Sodium hydrideHCID 69515632,2-Diethylpropanedioate

Product 1

HCID 705437787-Bromo-1,3-dihydro-5-(2-pyridyl)-2H-1,4-benzodiazepin-2-ylidenepropanedioic acid diethyl ester

Procedure

Diethylmalonate (45.55 ml) was added to THF (200 ml). The mixture was maintained at room temperature while sodium hydride (16 g of a 60% oil dispersion) was added over 1 hr. To the resulting suspension, diethyl chlorophosphate (14.45 ml) was added dropwise over 50 minutes. After a 30 minute agitation cycle, a THF solution of 7-bromo-1,3-dihydro-5-(2-pyridyl)-2H-1,4-benzodiazepin-2-one (15.8 g) was added dropwise over 20 minutes. The resulting solution was allowed to agitate for 1 hr. The pH was adjusted from 5.0 to 5.5, and the reaction solution was vacuum concentrated (40° C./30 mm) to remove the THF. To the residue was added cold water (600 ml) and hexane (100 ml). The crystalline solid obtained was filtered and washed with cold water and hexane. After the solid was dried to constant weight, the end product was obtained.

Workup

  1. additionwas added over 1 hr
  2. concentrationconcentrated (40° C./30 mm)
  3. customto remove the THF
  4. additionTo the residue was added cold water (600 ml) and hexane (100 ml)
  5. customThe crystalline solid obtained
  6. filtrationwas filtered
  7. washwashed with cold water and hexane
  8. customAfter the solid was dried to constant weight
  9. customthe end product was obtained

Sources & evidence

ORD record
ord-7a6e9d2072ba4ea5bc1c4efb374da6c0
Source dataset
uspto-grants-1982_06
Patent number
US04335042

Reaction notes

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