Reaktion #1998587

Reaktionsgleichung

N-ethyl-N-propan-2-ylpropan-2-amine

5-Chloro-N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-yl]pyrazine-2-carboxamide

(2R,6S)-1,2,6-trimethylpiperazine

2-[(2S,6R)-2,6-dimethylpiperazin-1-yl]acetonitrile

→

title compound

Ausbeute 22.0%

5-[(3R,5S)-4-(cyanomethyl)-3,5-dimethylpiperazin-1-yl]-N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-yl]pyrazine-2-carboxamide

Ausbeute 22.0%

Lösungsmittel

methanol

dimethylsulfoxide

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGthe solution was stirred at 60° C. for a further 2 h
2. 2
   Sonstigepurified by ion exchange chromatography
3. 3
   WaschenThe desired product was eluted from the column
4. 4
   Sonstigeto afford impure material
5. 5
   SonstigeThe concentrated eluent was purified by silica column chromatography
6. 6
   Wascheneluting with a gradient of 0 to 5% 7M NH3/MeOH in DCM
7. 7
   SonstigePure fractions were evaporated to dryness

Vorschrift

5-Chloro-N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-yl]pyrazine-2-carboxamide (271 mg, 0.70 mmol) was added in one portion to a 3:1 mixture of (2R,6S)-1,2,6-trimethylpiperazine and 2-[(2S,6R)-2,6-dimethylpiperazin-1-yl]acetonitrile (180 mg, 1.40 mmol) in anhydrous dimethylsulfoxide (1.40 ml) at 25° C. The resulting solution was stirred at ambient temperature for 2 h. The reaction was incomplete and N-ethyl-N-propan-2-ylpropan-2-amine (0.24 ml, 1.40 mmol) was added and the solution was stirred at 60° C. for a further 2 h. The reaction mixture was diluted with methanol (20 mL) and purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH to afford impure material. The concentrated eluent was purified by silica column chromatography, eluting with a gradient of 0 to 5% 7M NH3/MeOH in DCM. Pure fractions were evaporated to dryness to afford the title compound (77 mg, 22%) as a yellow solid.

Quelle