Sodium hydride → HCID 15586660, compound

HRID 2412993Notes

Reaction equation

HRID 2412993 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[CH:6][C:7]2[NH:13][C:12]3[N:14]=[CH:15][CH:16]=[CH:17][C:11]=3[N:10]=[C:9]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:8]=2[CH:24]=1.[H][H].Cl.[CH3:28][N:29]([CH3:34])[CH2:30][CH2:31][CH2:32]Cl.O.O.[C:37]([OH:42])(=[O:41])[C:38]([OH:40])=[O:39]>CN(C)C=O.C(O)(C)C.O>[C:37]([OH:42])(=[O:41])[C:38]([OH:40])=[O:39].[Cl:3][C:4]1[CH:5]=[CH:6][C:7]2[N:13]([CH2:32][CH2:31][CH2:30][N:29]([CH3:34])[CH3:28])[C:12]3[N:14]=[CH:15][CH:16]=[CH:17][C:11]=3[N:10]=[C:9]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:8]=2[CH:24]=1

Participants

9

Reactant 5

HCID 24758Sodium hydrideHCID 61373Oxalic acid dihydrateHCID 943083-(Dimethylamino)propyl chloride hydrochlorideHCID 135626398HCID 135626398, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 15586660HCID 15586660, compoundYield 71.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3776IsopropanolSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred suspension of 1.05 g (0.044 mole) of sodium hydride (in mineral oil) in 50 ml of anhydrous dimethylformamide, under nitrogen atmosphere was added, portionwise, 6.1 g (0.02 mole) of 8-chloro-6-phenyl-11H-pyrido[2,3-b][1,4]benzodiazepine. The reaction mixture was stirred at room temperature for 1.5 hr, during which evolution of hydrogen ceased. To the mixture was added, portionwise, 3.5 g (0.022 mole) of 3-dimethylaminopropylchloride hydrochloride. After stirring overnight at room temperature, the reaction mixture was poured into 1600 ml water and the combination extracted with three 250 ml portions of methylene chloride. The combined methylene chloride extract was washed with two 250 ml portions of water, dried over magnesium sulfate and evaporated under reduced pressure. The residue was dissolved in benzene and chromatographed with acetone-benzene on a 300 g column of florisil packed in benzene. Starting material, 1.6 g., was recovered in the benzene elution and 3.6 g. containing the product as free base was obtained from the acetone-benzene elution on evaporation of solvent. A portion of the crude free base, 2.5 g., was dissolved in hot isopropyl alcohol and reacted with 0.8 g (0.0064 mole) of oxalic acid dihydrate. The oxalate salt, which precipitated on cooling, was collected by filtration and recrystallized from ethanol to give 2.2 g product, m.p. 206°-208° C. Drying conditions prior to analyses were: 5 hr at 97°-98° C./0.02 mm Hg; over night at room temperature/0.02 mm Hg.

Workup

  1. additionunder nitrogen atmosphere was added
  2. additionTo the mixture was added
  3. extractionthe combination extracted with three 250 ml portions of methylene chloride
  4. extractionThe combined methylene chloride extract
  5. washwas washed with two 250 ml portions of water
  6. dry with materialdried over magnesium sulfate
  7. customevaporated under reduced pressure
  8. dissolutionThe residue was dissolved in benzene
  9. customchromatographed with acetone-benzene on a 300 g column of florisil
  10. custom, was recovered in the benzene elution and 3.6 g
  11. additioncontaining the product as free base
  12. customwas obtained from the acetone-benzene elution on evaporation of solvent
  13. customThe oxalate salt, which precipitated
  14. temperatureon cooling
  15. filtrationwas collected by filtration
  16. customrecrystallized from ethanol

Sources & evidence

ORD record
ord-97d99fd2ab8f445fba795e9bc8a5a83e
Source dataset
uspto-grants-1985_01
Patent number
US04495183

Reaction notes

Loading…