N-(3-(3-(Dimethylamino)-1-oxo-2-propenyl)phenyl)-N-ethylacetamide → Isozaleplon

HRID 1816523Notes

Reaction equation

HRID 1816523 reaction equation
CN(C)[CH:3]=[CH:4][C:5]([C:7]1[CH:8]=[C:9]([N:13]([CH2:17][CH3:18])[C:14](=[O:16])[CH3:15])[CH:10]=[CH:11][CH:12]=1)=O.[NH2:20][C:21]1[C:25]([C:26]#[N:27])=[CH:24][NH:23][N:22]=1>O.Cl>[C:26]([C:25]1[CH:24]=[N:23][N:22]2[CH:3]=[CH:4][C:5]([C:7]3[CH:8]=[C:9]([N:13]([CH2:17][CH3:18])[C:14](=[O:16])[CH3:15])[CH:10]=[CH:11][CH:12]=3)=[N:20][C:21]=12)#[N:27]

Participants

5

Reactant 2

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

Product 1

HCID 9879548IsozaleplonYield 1.6%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 962WaterSolvent

Procedure

N-[3-[3-(dimethylamino)-1-oxo-2-propenyl]phenyl]-N-ethylacetamide (5.2 g, 0.02 mol) and 3-amino-4-cyanopyrazole (2.16 g, 0.02 mol) were dissolved in the mixture of water (50 ml) and concentrated hydrochloric acid (40 ml) and the mixture was stirred at room temperature for 8 h. The reaction mixture was then cooled to 5° C. and the precipitate was removed by filtration. The filtrate was neutralized by concentrated aqueous ammonia solution to precipitate 380 mg of the mixture of zaleplon and its regioisomer 4 which was collected by filtration. The filtrate was extracted with 100 ml of ethylacetate to give 100 mg of the mixture of the above two compounds upon evaporation. The two crops combined were put to a silica gel column (100 g) and the elution was performed by the solvent mixture of chloroform and acetone 3:1 (v/v) to yield as a second crop 240 mg (4%) of 4; mp 194-196° C.; 1H-NMR (CDCl3) δ (ppm) 1.143 (t, 3H), 1.876 (s, 3H), 3.804 (q, 2H), 7.361 (d, 1H), 7.532 (d, 1H), 7.613 (t, 1H), 8.018 (s, 1H), 8.159 ( d, 1H), 8.375 (s, 1H), 8.805 ((d, 1H); 13C-NMR (CDCl3) δ (ppm) 12.89, 22.68, 43.84, 83.17, 107.71, 112.84, 127.17, 127.48, 130.62, 131.63, 136.67, 137.46, 144.10, 148.31, 149.99, 158.60, 169.90; MS (EI, 70 EV) m/z (%) 305 (M+, 18), 248 (59).

Workup

  1. temperatureThe reaction mixture was then cooled to 5° C.
  2. customthe precipitate was removed by filtration
  3. customto precipitate 380 mg of the mixture of zaleplon and its regioisomer 4 which
  4. filtrationwas collected by filtration
  5. extractionThe filtrate was extracted with 100 ml of ethylacetate

Sources & evidence

ORD record
ord-447072f660c44073805fdeb6f8210c8b
Source dataset
uspto-grants-2005_04
Patent number
US06884888B2

Reaction notes

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