反应 #70645

反应方程式

4-[1-(6-Chloro-4-cyclopropoxy-pyrido[3,2-d]pyrimidin-2-ylamino)-ethyl]-benzenesulfonamide

Ethynyl-cyclopropane

water

→

desired product

收率 77.7%

(R)-4-(1-(4-cyclopropoxy-6-(2-cyclopropylethynyl)pyrido[3,2-d]pyrimidin-2-ylamino)ethyl)benzenesulfonamide

收率 77.7%

溶剂

—

TEA

DMF

反应条件

后处理

1. 1
   其他was degassed for 10 min
2. 2
   其他then purged with argon
3. 3
   其他the reaction tube was sealed
4. 4
   温度After cooling to room temperature
5. 5
   萃取extracted twice with EtOAc
6. 6
   洗涤The combined organic layers were washed with 5% LiCl solution and brine
7. 7
   其他Solvent was removed by concentration in vacuo
8. 8
   其他the residue was purified by RP HPLC

实验过程

A mixture of 4-[1-(6-Chloro-4-cyclopropoxy-pyrido[3,2-d]pyrimidin-2-ylamino)-ethyl]-benzenesulfonamide (300 mg, 0.71 mmol), PdCl2(PPh3)2 (25 mg, 0.035 mmol), CuI (13.5 mg, 0.07 mmol) in TEA (1 mL) and DMF (5 mL) was degassed for 10 min then purged with argon. Ethynyl-cyclopropane (0.3 mL, 3.5 mmol) was added and the reaction tube was sealed and heated at 80° C. for 3 hours. After cooling to room temperature, the reaction mixture was poured into water and extracted twice with EtOAc. The combined organic layers were washed with 5% LiCl solution and brine. Solvent was removed by concentration in vacuo and the residue was purified by RP HPLC using a C18 column with a gradient of H2O, 0.1% TFA-acetonitrile, to provide 248 mg (62%) of desired product. MS (m/z) 450.0 [M+H]+; HPLC Rt=2.16 min.

来源