Réaction #4935

Équation de réaction

pyrazole

sodium hydride

pyrazole

pyrazole

2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f][1,4]oxazepine-5(4H)-one

sodium hydride

→

2,3-Dihydro-4-methyl-2-[2-(1H-pyrazol-1-yl)ethyl]pyrido[3,2-f][1,4]oxazepin-5(4H)-one

Solvants

dimethylformamide

dimethylformamide

dimethylformamide

dimethylformamide

Conditions de réaction

Traitement

1. 1
   AutreThe flask was sealed
2. 2
   workup.ADDITIONwas added to the reaction solution
3. 3
   workup.STIRRINGstirred overnight
4. 4
   workup.ADDITIONwas added
5. 5
   workup.STIRRINGthe reaction stirred overnight
6. 6
   AutreDimethylformamide was removed by rotary evaporation (80° C., vacuum pump)
7. 7
   Lavagewas washed with dilute aqueous sodium hydroxide (1×50 ml)
8. 8
   Séchagedried over anhydrous sodium sulfate
9. 9
   Concentrationconcentrated by rotary evaporation (70° C., water aspirator)
10. 10
    AutreThe material was purified by high pressure liquid chromatography, 95:5 by volume ethanol
11. 11
    workup.ADDITIONThe fractions containing the desired product
12. 12
    Concentrationwere concentrated by rotary evaporation (70° C., water aspirator)
13. 13
    AutreCrystallization
14. 14
    Températureupon cooling
15. 15
    AutreThe crystals were collected
16. 16
    Autrerecrystallized from ethanol

Mode opératoire

To a suspension of sodium hydride (1.2 g active, 0.05 mole) in dimethylformamide (15 ml) was added dropwise a solution of pyrazole (3.10 g, 0.045 mole) in dimethylformamide (15 ml). The resulting solution was then added to a solution of 2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f][1,4]oxazepine-5(4H)-one (9.12 g, 0.038 mole) in 30 ml of dimethylformamide. The flask was sealed and stirred overnight. Because the reaction had not yet gone to completion at this point, pyrazole (3.12 g, 0.045 mole) was added to the reaction solution and stirred overnight. The reaction was still not complete and another suspension of sodium hydride (0.5 g active, 0.021 mole) and pyrazole (1.5 g, 0.022 mole) in dimethylformamide (10 ml) was added and the reaction stirred overnight. The reaction appeared to be complete. Dimethylformamide was removed by rotary evaporation (80° C., vacuum pump), and the residue taken up in chloroform (100 ml) which was washed with dilute aqueous sodium hydroxide (1×50 ml), dried over anhydrous sodium sulfate and concentrated by rotary evaporation (70° C., water aspirator). The material was purified by high pressure liquid chromatography, 95:5 by volume ethanol:methanol on a silica gel column. The fractions containing the desired product were concentrated by rotary evaporation (70° C., water aspirator). Crystallization ensued upon cooling. The crystals were collected and recrystallized from ethanol. The yield was 1.5 (14.5%), m.p. 132°-134° C.

Source