Oxygen → Zaleplon

HRID 1782393Notes

Reaction equation

HRID 1782393 reaction equation
O=O.C[N:4]([CH3:21])[CH:5]=[CH:6][C:7]([C:9]1[CH:10]=[C:11]([N:15]([CH2:19][CH3:20])[C:16](=[O:18])[CH3:17])[CH:12]=[CH:13][CH:14]=1)=O.N[C:23]1[C:27]([C:28]#[N:29])=C[NH:25][N:24]=1>O>[CH3:20][CH2:19][N:15]([C:16]([CH3:17])=[O:18])[C:11]1[CH:12]=[CH:13][CH:14]=[C:9]([C:7]2[N:25]3[N:24]=[CH:23][C:27]([C:28]#[N:29])=[C:21]3[N:4]=[CH:5][CH:6]=2)[CH:10]=1

Participants

5

Reactant 3

HCID 977OxygenHCID 53395302N-(3-(3-(Dimethylamino)-1-oxo-2-propenyl)phenyl)-N-ethylacetamideHCID 178510443HCID 178510443, compound

Product 1

HCID 5719ZaleplonYield 91%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

WO O2/100828 A2 discloses a further improvement in the '538 process by reacting the same intermediates, N-[3-[3-(dimethylamino)-1-oxo-2-propenyl]phenyl]-N-ethylacetamide and 3-amino-4-cyanopyrazole, in a liquid medium of water and a water-miscible organic compound under acidic conditions. Although the reaction is claimed to proceed through an imine intermediate that was prone to precipitate from water, the imine intermediate remained dissolved in the reaction media. It is stated in the '828 patent that the process proceeds rapidly at ambient temperature to produce zaleplon with a 91-97% yield having a purity ranging from 98.7 to 99.5% according the HPLC analysis. The method minimized the formation of a regioisomer by-product, N-[3-(3-cyanopyrazolo[1,5-a]pyrimidin-5-yl)phenyl]-N-ethylacetamide which is favored under excess acid conditions.

Workup

  1. customto precipitate from water
  2. dissolutionthe imine intermediate remained dissolved in the reaction media
  3. customproceeds rapidly at ambient temperature

Sources & evidence

ORD record
ord-0e8c1bb6a9204f87b65d9dd37506e727
Source dataset
uspto-grants-2009_03
Patent number
US07498434B2

Reaction notes

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