반응 #168000

반응 방정식

Cs2CO3

5-isopropyl-2-methylphenyl trifluoromethanesulfonate

2-(2,6-dimethylphenyl)-4-(3-methoxypropoxy)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

→

2-(2,6-dimethylphenyl)-6-(5-isopropyl-2-methylphenyl)-4-(3-methoxypropoxy)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

용매

THF

ethyl acetate

water

반응 조건

후처리

1. 1
   기타the reaction mixture was degassed via a series of argon/vacuum cycles
2. 2
   기타The vessel was then sealed
3. 3
   온도The reaction was then cooled to room temperature
4. 4
   기타The layers were separated
5. 5
   추출the aqueous layer was extracted once with ethyl acetate
6. 6
   건조dried over Na2SO4
7. 7
   여과filtered
8. 8
   농축concentrated
9. 9
   기타The resulting residue was purified by silica gel flash chromatography (5-50% ethyl acetate/heptanes)

실험 절차

To 5-isopropyl-2-methylphenyl trifluoromethanesulfonate, prepared as described in Example 15 (153 mg, 0.541 mmol) in a microwave vial was added a solution of 2-(2,6-dimethylphenyl)-4-(3-methoxypropoxy)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine in THF (4 mL). Next, Cs2CO3 (235 mg, 0.721 mmol) was added and the reaction mixture was degassed via a series of argon/vacuum cycles. The reaction mixture was then charged with chloro(2-dicyclohxylphosphino-2′,4′,6%-triisopropyl-1,1′-biphenyl)-[2-(2-aminoethyl)phenyl)]-palladium(II) (CAS#1028206-56-5, 26.6 mg, 0.036 mmol). The vessel was then sealed and heated via microwave irradiation at 140° C. for 90 minutes. The reaction was then cooled to room temperature and diluted with ethyl acetate and water. The layers were separated and the aqueous layer was extracted once with ethyl acetate. The organic layers were combined, dried over Na2SO4 filtered and concentrated. The resulting residue was purified by silica gel flash chromatography (5-50% ethyl acetate/heptanes) to provide 2-(2,6-dimethylphenyl)-6-(5-isopropyl-2-methylphenyl)-4-(3-methoxypropoxy)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine. 1H NMR (400 MHz, CD2Cl2) δ ppm 1.25 (d, J=7.1 Hz, 6 H) 2.08 (quin, J=6.3 Hz, 2 H) 2.28 (s, 6 H) 2.49 (s, 3 H) 2.92 (dt, J=13.8, 6.9 Hz, 1 H) 3.28 (s, 3 H) 3.49 (t, J=5.9 Hz, 2 H) 3.58 (t, J=5.7 Hz, 2 H) 3.81 (t, J=5.6 Hz, 2 H) 4.37 (s, 2 H) 4.71 (t, J=6.4 Hz, 2 H) 7.12 (dd, J=7.7, 1.4 Hz, 1 H) 7.17 (s, 1 H) 7.20-7.27 (m, 3 H) 7.36-7.41 (m, 1 H); MS (ESI+) m/z 460.4 (M+H)+.

출처