Reaktion #1018393

Reaktionsgleichung

triethylamine

2-(1-methyl-1H-pyrazol-5-yl)acetonitrile

acetyl chloride

Acetic acid

(R)-(1-(5,6-diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochloride

→

title compound

(R)-(1-(2-(1-(1-Methyl-1H-pyrazol-5-yl)cyclopropyl)-3H-imidazo[4,5-b]pyridin-5-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone

Lösungsmittel

ethanol

ethanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe solvent was removed under a stream of nitrogen
2. 2
   workup.ADDITIONEthanol (0.5 mL) was added to the residue
3. 3
   Temperaturthe reaction mixture was heated in the microwave for 45 min at 130° C
4. 4
   SonstigeThe solvent was removed under a stream of nitrogen
5. 5
   workup.ADDITIONEthyl acetate (10 mL) was added to the residue
6. 6
   WaschenThe solution was washed with aqueous sodium hydroxide (1N, 3 mL)
7. 7
   Waschenwashed with water (3 mL)
8. 8
   Waschenwashed with brine (3 mL)
9. 9
   Trocknendried over magnesium sulfate
10. 10
    Filtrationfiltered
11. 11
    Einengenconcentrated under reduced pressure
12. 12
    SonstigeThe crude material was purified via HPLC

Vorschrift

To a solution of 2-(1-methyl-1H-pyrazol-5-yl)acetonitrile (14.5 mg, 0.10 mmol) in ethanol (150 μL, 2.6 mmol) was added acetyl chloride (110 μL, 1.5 mmol). The reaction mixture was stirred at room temperature for 16 h. The solvent was removed under a stream of nitrogen. Ethanol (0.5 mL) was added to the residue followed by a solution of (R)-(1-(5,6-diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochloride (36 mg, 0.01 mmol) and triethylamine (70 μL, 0.50 mmol) in ethanol (1 mL). Acetic acid (100 μL, 1.75 mmol) was added and the reaction mixture was heated in the microwave for 45 min at 130° C. The solvent was removed under a stream of nitrogen. Ethyl acetate (10 mL) was added to the residue. The solution was washed with aqueous sodium hydroxide (1N, 3 mL), washed with water (3 mL), washed with brine (3 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude material was purified via HPLC to afford the title compound. MS (ESI+) (M+H) 420.3; HPLC retention time 1.88 min (Method B).

Quelle