反応 #1492238

反応方程式

4-chloro-6-methyl-5-(6-amino-pyridin-3-ylethynyl)-pyrimidin-2-ylamine

4-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

Na2CO3

LiCl

→

desired product

収率 82.1%

4-[2-Amino-5-(6-amino-pyridin-3-ylethynyl)-6-methyl-pyrimidin-4-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

収率 82.1%

溶媒

toluene ethanol

反応条件

後処理

1. 1
   温度at reflux
2. 2
   温度After cooling the solvent
3. 3
   その他is evaporated
4. 4
   workup.ADDITIONwater is added
5. 5
   抽出the aqueous suspension is extracted 4 times with ethyl acetate (200 mL each)
6. 6
   乾燥The organic layer is dried over MgSO4
7. 7
   その他the solvent is removed under reduced pressure
8. 8
   その他The residue is purified

実験手順

A mixture of 500 mg (1.9 mmol) 4-chloro-6-methyl-5-(6-amino-pyridin-3-ylethynyl)-pyrimidin-2-ylamine, 1.2 g (3.9 mmol) 4-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester, 135 mg (1.9 mmol) Pd(PPh3)2Cl2, 40 mL 1 M aqueous Na2CO3 solution and 244 mg LiCl (5.78 mmol) in 100 mL toluene/ethanol (4:1 v/v) is kept over 2 days at reflux. After cooling the solvent is evaporated, water is added and the aqueous suspension is extracted 4 times with ethyl acetate (200 mL each). The organic layer is dried over MgSO4 and the solvent is removed under reduced pressure. The residue is purified using flash column chromatography yielding 635 mg (1.56 mmol) of the desired product which is used without further purification in the next step.

出典