Nordiazepam → Pinazepam

HRID 1446803Notes

Reaction equation

HRID 1446803 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:11][C:10](=[O:12])[CH2:9][N:8]=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:6]=2[CH:19]=1.[Na].CN(C)C=O.[CH2:26](Br)[C:27]#[CH:28]>C[O-].[Na+].CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH2:28][C:27]#[CH:26])[C:10](=[O:12])[CH2:9][N:8]=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:6]=2[CH:19]=1

Participants

7

Reactant 4

HCID 2997NordiazepamHCID 6228DimethylformamideHCID 7842Propargyl bromideHCID 5360545Sodium

Product 1

HCID 40391Pinazepam

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 10942334Sodium MethoxideSolvent

Procedure

100 ml. of a 1 N solution in sodium methoxide in methanol were added to a solution of 27.05 g (0.1 mol) of 7-chloro-2,3-dihydro-5-phenyl-1H-1,4-benzodiazepin-2-one in 500 ml. of anhydrous methanol. The solvent was driven off under reduced pressure, and the resulting sodium derivative was dissolved in 200 ml. of dimethylformamide. The temperature of the solution was maintained at 10°-15° C. while 10 ml. of propargyl bromide were added dropwise; and the mixture was stirred for about 4 hours, and then poured over ice. The product was filtered and dissolved in chloroform; and the chloroform solution was separated from the aqueous layer and dried over sodium sulphate. The chloroform was evaporated off from the solution, and the residue was dissolved in the minimum quantity of a 7:3 (by volume) mixture of benzene and ethyl acetate. This solution was chromatographed on a column of silica gel and eluted with a 7:3 (by volume) mixture of benzene and ethyl acetate. The portion of eluate containing the desired product, as determined by thin-layer chromatography, was collected and evaporated under reduced pressure. The residue was recrystallized from a 1:1 (by volume) mixture of benzene and hexane, giving 14 g of the pure desired product with a melting point of 141°-143° C.

Workup

  1. temperatureThe temperature of the solution was maintained at 10°-15° C. while 10 ml
  2. additionpoured over ice
  3. filtrationThe product was filtered
  4. dissolutiondissolved in chloroform
  5. customand the chloroform solution was separated from the aqueous layer
  6. dry with materialdried over sodium sulphate
  7. customThe chloroform was evaporated off from the solution
  8. dissolutionthe residue was dissolved in the minimum quantity of a 7:3 (by volume) mixture of benzene and ethyl acetate
  9. customThis solution was chromatographed on a column of silica gel
  10. washeluted with a 7:3 (by volume) mixture of benzene and ethyl acetate
  11. additionThe portion of eluate containing the desired product
  12. customwas collected
  13. customevaporated under reduced pressure
  14. customThe residue was recrystallized from a 1:1 (by volume) mixture of benzene and hexane

Sources & evidence

ORD record
ord-1af62056e6e34c1a80dae170db51ad53
Source dataset
uspto-grants-1982_02
Patent number
US04313943

Reaction notes

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