反応 #535753

反応方程式

8a

4-(6-Chloro-5-methoxy-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester

cesium carbonate

5-Methanesulfonyl-2,3-dihydro-1H-indole

tri-t-butylphosphonium tetrafluoroborate

→

4-[6-(5-Methanesulfonyl-2,3-dihydro-indol-1-yl)-5-methoxy-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester

溶媒

dioxane

dioxane

反応条件

後処理

1. 1
   温度The mixture cooled to room temperature
2. 2
   ろ過the mixture was filtered
3. 3
   洗浄washed with DCM
4. 4
   濃縮The filtrate was concentrated under a stream of nitrogen
5. 5
   その他was purified by preparative HPLC
6. 6
   その他to afford 8-1

実験手順

A mixture of 8a (49 mg, 0.15 mmol), cesium carbonate (0.11 g, 2 eq), 5-Methanesulfonyl-2,3-dihydro-1H-indole (35 mg, 1.2 eq), tris(dibenzylideneacetone)-dipalladium (31 mg, 0.1 eq), tri-t-butylphosphonium tetrafluoroborate (37 mg, 0.8 eq) and dioxane (1.5 mL) was heated at 90° C. for 4 h. The mixture cooled to room temperature, dioxane was added and the mixture was filtered and washed with DCM. The filtrate was concentrated under a stream of nitrogen and the residue was taken up in 1 mL of THF and was purified by preparative HPLC to afford 8-1; LCMS 491.2 (MH+), tR=5.35 (Method 6). EC50: 201 nM.

出典