反応 #70645

反応方程式

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

Ethynyl-cyclopropane

water

→

desired product

収率 77.7%

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

収率 77.7%

溶媒

—

TEA

DMF

反応条件

後処理

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

実験手順

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.

出典