Reaktion #159884

Reaktionsgleichung

(4,6-dichloropyrimidin-5-yl)[1-methyl-5-(4-methylphenyl)-1H-pyrazol-4-yl]methanone

N,N-diisopropylethylamine

{4-chloro-6-[(3S)-3-(piperidin-1-yl)pyrrolidin-1-yl]pyrimidin-5-yl}[1-methyl-5-(4-methylphenyl)-1H-pyrazol-4-yl]methanone

methylhydrazine

1-[(3S)-pyrrolidin-3-yl]piperidine

→

product

Ausbeute 90.0%

1-Methyl-3-[1-methyl-5-(4-methylphenyl)-1H-pyrazol-4-yl]-4-[(3S)-3-(piperidin-1-yl)pyrrolidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine

Ausbeute 90.0%

Lösungsmittel

acetonitrile

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe resulting reaction mixture
2. 2
   workup.STIRRINGAfter being stirred overnight at room temperature
3. 3
   Einengenthe reaction mixture was concentrated in vacuo
4. 4
   Sonstigepartitioned between dichloromethane (100 mL) and water (100 mL)
5. 5
   ExtraktionThe aqueous layer was extracted with dichloromethane (2×100 mL)
6. 6
   TrocknenThe combined organic layers were dried over sodium sulfate
7. 7
   Filtrationfiltered
8. 8
   Einengenconcentrated
9. 9
   Sonstigepurification via silica gel chromatography (Gradient: 10% to 50% ethyl acetate in petroleum ether)

Vorschrift

To a mixture of (4,6-dichloropyrimidin-5-yl)[1-methyl-5-(4-methylphenyl)-1H-pyrazol-4-yl]methanone (C5) (7.3 g, 21 mmol) and N,N-diisopropylethylamine (13.56 g, 104.9 mmol) in acetonitrile (100 mL) was added 1-[(3S)-pyrrolidin-3-yl]piperidine (4.8 g, 31 mmol), and the resulting reaction mixture was stirred at room temperature for 3 hours. To this solution of {4-chloro-6-[(3S)-3-(piperidin-1-yl)pyrrolidin-1-yl]pyrimidin-5-yl}[1-methyl-5-(4-methylphenyl)-1H-pyrazol-4-yl]methanone (C7) was added drop-wise a solution of methylhydrazine (12.1 g, 262 mol) in acetonitrile (20 mL). After being stirred overnight at room temperature, the reaction mixture was concentrated in vacuo and partitioned between dichloromethane (100 mL) and water (100 mL). The aqueous layer was extracted with dichloromethane (2×100 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated; purification via silica gel chromatography (Gradient: 10% to 50% ethyl acetate in petroleum ether) afforded the product as a white solid. Yield: 8.64 g, 18.9 mmol, 90% yield. LCMS m/z 457.3 (M+1). 1H NMR (400 MHz, CDCl3) δ 1.39-1.49 (br m, 2H), 1.53-1.73 and 2.00-2.25 (br multiplets, presumed 8H), 2.31 (s, 3H), 2.32-2.45 (br m, 2H), 2.56-2.68 (br m, 1H), 2.90-3.16 (v br m, 1H), 3.26-3.78 (br m, 3H), 3.87 (s, 3H), 4.00 (s, 3H), 7.16 (br AB quartet, JAB=8 Hz, ΔνAB=26 Hz, 4H), 7.66 (s, 1H), 8.29 (s, 1H).

Quelle