Reaktion #948248

Reaktionsgleichung

1-tert.-butoxycarbonylpiperazine

N-methyl morpholine

5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazole-3-carboxylic acid, monohydrate

1-hydroxybenzotriazole hydrate

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride

→

1,1-dimethylethyl 4-[[5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]carbonyl]-1-piperazinecarboxylate

Ausbeute 78.4%

Lösungsmittel

ethyl acetate

NaHCO3

isopropyl alcohol toluene

dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGThe reaction was stirred from 0° C. to room temperature overnight
2. 2
   Extraktionextracted
3. 3
   WaschenThe organic layer was washed with water and brine
4. 4
   Sonstigedried over MGSO4
5. 5
   FiltrationAfter filtration
6. 6
   Sonstigethe solvent was removed under reduced pressure
7. 7
   Sonstigecrude product was obtained (1.7595 g)

Vorschrift

In a solution of 5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazole-3-carboxylic acid, monohydrate (0.9905 g, 3.5 mmol) from step 1 and 1-hydroxybenzotriazole hydrate (0.4824 g, 3.57 mmol) in dimethylformamide (20 mL) at 0° C. under N2, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.6983 g, 3.57 mmol) was added. The solution was stirred at 0° C. under N2 for 1 hour, then was added 1-tert.-butoxycarbonylpiperazine (0.6585 g, 3.5 mmol) followed by N-methyl morpholine (0.40 mL, 3.6 mmol). The reaction was stirred from 0° C. to room temperature overnight. The reaction mixture was diluted with ethyl acetate and saturated NaHCO3 solution, extracted. The organic layer was washed with water and brine, and dried over MGSO4. After filtration, the solvent was removed under reduced pressure, and crude product was obtained (1.7595 g). The desired product 1,1-dimethylethyl 4-[[5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]carbonyl]-1-piperazinecarboxylate (1.2375 g, 78.4%) was isolated by chromatography (silica gel, 10:90 isopropyl alcohol/toluene). Anal. Calc'd for C24H26N5FO3: C, 63.85; H, 5.80; N, 15.51; Found: C, 63.75; H, 5.71; N, 15.16. MS (MH+): 452 (base peak).

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