反応 #48153

反応方程式

Potassium carbonate

(4,4-difluoro-piperidin-1-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-methanone

(4,4-Difluoro-piperidin-1-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-methanone

intermediate 1

(4,4-Difluoro-piperidin-1-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-methanone

5-bromopyrimidine

trans-1,2-diaminocyclohexane

potassium phosphate tribasic

→

desired product

(4,4-Difluoro-piperidin-1-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1-pyrimidin-5-yl-1H-indol-2-yl]-methanone

溶媒

dioxan

反応条件

後処理

1. 1
   温度under reflux for 3 d
2. 2
   温度the mixture was refluxed for 1 d
3. 3
   その他evaporated to dryness
4. 4
   その他purified on silica gel
5. 5
   洗浄eluting with a 49:1:0 to 95:5:0.25 gradient of dichloromethane/methanol/ammonium hydroxide

実験手順

A mixture of (4,4-difluoro-piperidin-1-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-methanone (intermediate 1, 100 mg, 1.0 eq.), 5-bromopyrimidine (44 mg, 1.1 eq.), trans-1,2-diaminocyclohexane (18 mg, 0.65 eq.), copper(I) iodide (6 mg, 0.12 eq.) and potassium phosphate tribasic (110 mg, 2.1 eq.) in dioxan (2.0 mL) was stirred under reflux for 3 d. Potassium carbonate (72 mg, 2.1 eq.) was added and the mixture was refluxed for 1 d, evaporated to dryness and purified on silica gel, eluting with a 49:1:0 to 95:5:0.25 gradient of dichloromethane/methanol/ammonium hydroxide, to yield 121 mg (100%) from the desired product as orange oil. MS (m/e): 484.4 (MH+, 100%).

出典