Nordiazepam → Pinazepam

HRID 1446802Notes

Reaction equation

HRID 1446802 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[CH:6][C:7]2[NH:13][C:12](=[O:14])[CH2:11][N:10]=[C:9]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:8]=2[CH:21]=1.[CH2:22](Br)[C:23]#[CH:24]>CN(C)C=O>[Cl:3][C:4]1[CH:5]=[CH:6][C:7]2[N:13]([CH2:24][C:23]#[CH:22])[C:12](=[O:14])[CH2:11][N:10]=[C:9]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:8]=2[CH:21]=1

Participants

5

Reactant 3

HCID 2997NordiazepamHCID 7842Propargyl bromideHCID 24758Sodium hydride

Product 1

HCID 40391Pinazepam

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

3.76 g of 50% sodium hydride in mineral oil were added to 250 ml. of dimethylforamamide cooled to about 0° C. The temperature of the suspension was maintained at about 0° C., while a solution of 27.05 g (0.1 mol) of 7-chloro-2,3-dihydro-5-phenyl-1H-1,4-benzodiazepin-2-one in 50 ml. of dimethylformamide was added dropwise to it. The resulting mixture was stirred for 2 hours, and then 10 ml. of propargyl bromide were added dropwise while maintaining the temperature at 10°-15° C. The reaction 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 16 g of the pure desired product with a melting point of 141°-143° C.

Workup

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

Sources & evidence

ORD record
ord-9f963bf19e674272ab493f1aad8bff74
Source dataset
uspto-grants-1982_02
Patent number
US04313943

Reaction notes

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