反応 #2276515

反応方程式

Methyl-2-butynoate

(5-Bromo-2-chloro-pyrimidin-4-yl)cyclopentylamine

lithium chloride

potassium carbonate

→

2-chloro-7-cyclopentyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid methyl ester

収率 25.0%

溶媒

DMF

反応条件

後処理

1. 1
   workup.ADDITIONback-filled
2. 2
   workup.ADDITIONfilled with nitrogen three times
3. 3
   温度After cooling to room temperature the solution
4. 4
   ろ過is filtered through Celite
5. 5
   workup.ADDITIONdiluted with water
6. 6
   抽出extracted with ethyl acetate three times
7. 7
   洗浄washed with brine
8. 8
   乾燥dried over anhydrous sodium sulfate
9. 9
   その他The solvent is evaporated
10. 10
    その他the crude product is purified

実験手順

A solution of (5-Bromo-2-chloro-pyrimidin-4-yl)cyclopentylamine (8 g, 28.93 mmol), lithium chloride (1.23 g, 28.9 mmol), potassium carbonate (10 g, 72 mmol) and palladium acetate (324.68 mg, 1.45 mmol) in DMF (300 mL) is degassed and back-filled filled with nitrogen three times. Methyl-2-butynoate (8.5 mL, 87 mmol) is added and the reaction solution is heated at 120° C. for 5 h. LC-MS indicated the formation of two regioisomers and no starting material remaining. After cooling to room temperature the solution is filtered through Celite, diluted with water and extracted with ethyl acetate three times. The organic layers are combined, washed with brine and dried over anhydrous sodium sulfate. The solvent is evaporated and the crude product is purified using silica gel chromatography (˜20% ethyl acetate/80% hexane) to give 2-chloro-7-cyclopentyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid methyl ester as a yellow solid (2.11 g, 25%). [M+H]+=294.04.

出典