반응 #70645

반응 방정식

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

Ethynyl-cyclopropane

water

→

desired product

수율 77.7%

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

수율 77.7%

용매

—

TEA

DMF

반응 조건

후처리

1. 1
   기타was degassed for 10 min
2. 2
   기타then purged with argon
3. 3
   기타the reaction tube was sealed
4. 4
   온도After cooling to room temperature
5. 5
   추출extracted twice with EtOAc
6. 6
   세척The combined organic layers were washed with 5% LiCl solution and brine
7. 7
   기타Solvent was removed by concentration in vacuo
8. 8
   기타the residue was purified by RP HPLC

실험 절차

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.

출처