碳酸氢铯 → 2-(2,6-Dimethylphenyl)-6-(5-isopropyl-2-methylphenyl)-4-(3-methoxypropoxy)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

HRID 80818

反应方程式

HRID 80818 反应方程式
FC(F)(F)S(O[C:7]1[CH:12]=[C:11]([CH:13]([CH3:15])[CH3:14])[CH:10]=[CH:9][C:8]=1[CH3:16])(=O)=O.[CH3:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([CH3:26])[C:21]=1[C:27]1[N:28]=[C:29]([O:37][CH2:38][CH2:39][CH2:40][O:41][CH3:42])[C:30]2[CH2:36][NH:35][CH2:34][CH2:33][C:31]=2[N:32]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1COCC1.C(OCC)(=O)C.O.[Pd+2]>[CH3:26][C:22]1[CH:23]=[CH:24][CH:25]=[C:20]([CH3:19])[C:21]=1[C:27]1[N:28]=[C:29]([O:37][CH2:38][CH2:39][CH2:40][O:41][CH3:42])[C:30]2[CH2:36][N:35]([C:7]3[CH:12]=[C:11]([CH:13]([CH3:15])[CH3:14])[CH:10]=[CH:9][C:8]=3[CH3:16])[CH2:34][CH2:33][C:31]=2[N:32]=1

参与物

8

反应物 3

HCID 10796碳酸氢铯HCID 130964092-Methyl-5-(propan-2-yl)phenyl trifluoromethanesulfonateHCID 712388462-(2,6-Dimethylphenyl)-4-(3-methoxypropoxy)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

产物 1

HCID 712448102-(2,6-Dimethylphenyl)-6-(5-isopropyl-2-methylphenyl)-4-(3-methoxypropoxy)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

试剂、催化剂与溶剂 4

HCID 105144烯丙基氯化[1,3-双(2,6-二异丙基苯)咪唑-2-基]钯催化剂HCID 962聚[6-[4-(4-氰基苯基)苯氧基]己基甲基丙烯酸酯]溶剂HCID 8028四氢呋喃溶剂HCID 8857乙酸乙酯溶剂

反应条件

温度
140 °C

实验过程

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)+.

后处理

  1. customthe reaction mixture was degassed via a series of argon/vacuum cycles
  2. customThe vessel was then sealed
  3. temperatureThe reaction was then cooled to room temperature
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted once with ethyl acetate
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resulting residue was purified by silica gel flash chromatography (5-50% ethyl acetate/heptanes)

来源与证据

ORD记录
ord-eb7f4b021966485db8d11a782f60e82d
来源数据集
uspto-grants-2014_09
专利号
US08846656B2

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