Reaktion #43204

Reaktionsgleichung

Intermediate 125

Methanesulfonic acid 3-(2-chloro-pyrimidin-4-yl)-benzyl ester

Methanesulfonic acid 3-(2-chloro-pyrimidin-4-yl)-benzyl ester

Intermediate 127

2-(R)-Methyl-piperazine-1-carboxylic acid tert-butyl ester

2-(R)-Methyl-piperazine-1-carboxylic acid tert-butyl ester

diisopropylethylamine

→

oily product

Ausbeute 53.0%

4-[3-(2-Chloro-pyrimidin-4-yl)-benzyl]-2-(R)-methyl-piperazine-1-carboxylic acid tert-butyl ester

Ausbeute 53.0%

Lösungsmittel

ethylene glycol dimethyl ether

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeevaporated under reduced pressure
2. 2
   workup.DISSOLUTIONthe residue was dissolved in dichloromethane
3. 3
   Waschenwashed with water (3×), brine
4. 4
   Sonstigedried
5. 5
   Trocknenover dried over Na2SO4
6. 6
   Sonstigechromatographed on silica gel (dichloromethane:methanol=98:2)

Vorschrift

Intermediate 125 Methanesulfonic acid 3-(2-chloro-pyrimidin-4-yl)-benzyl ester (0.70 g) and Intermediate 127 2-(R)-Methyl-piperazine-1-carboxylic acid tert-butyl ester (0.61 g) with diisopropylethylamine (0.70 mL) in ethylene glycol dimethyl ether (20 mL) was refluxed for 3 hours, cooled to room temperature, evaporated under reduced pressure and the residue was dissolved in dichloromethane, washed with water (3×), brine, dried over dried over Na2SO4, chromatographed on silica gel (dichloromethane:methanol=98:2) to give 0.50 g of oily product with yield 53%. LC-MS showed the product had the expected M+H+ of 403. 1H NMR (Varian 300 MHz, CDCl3, shifts relative to the solvent peak at 7.24 ppm) δ 8.6 (s, 1H) 8.0 (s, 1H) 7.9 (d, 1H) 7.6 (d, 1H) 7.5 (m, 2H) 4.2 (S, 1 h) 3.8 (d, 1H) 3.4 (m, 2H) 3.0 (m, 1H) 2.7 (d, 1H), 2.6 (d, 1H) 2.1 (m, 2H) 1.4 (s, 9H) 1.2 (d, 3H).

Quelle