반응 #1872320

반응 방정식

DMF

4-[3-({4-[(5-Chloro-7-iodo-1,3-benzodioxol-4-yl)amino]-6-methoxyquinazolin-7-yl}oxy)propyl]-1-methylpiperazin-2-one

N,N-dimethyl-N′-prop-2-yn-1-ylurea

N,N-dimethyl-N′-prop-2-yn-1-ylurea

diisopropylamine

→

title compound

수율 66.0%

N′-{3-[6-Chloro-7-({6-methoxy-7-[3-(4-methyl-3-oxopiperazin-1-yl)propoxy]quinazolin-4-yl}amino)-1,3-benzodioxol-4-yl]prop-2-yn-1-yl}-N,N-dimethylurea

수율 66.0%

용매

ethyl acetate

반응 조건

후처리

1. 1
   기타reaction
2. 2
   온도heated at 60° for 3 hr
3. 3
   온도heating
4. 4
   workup.WAITcontinued for 3 hr
5. 5
   기타The mixture was then evaporated
6. 6
   기타the residue partitioned between water and dichloromethane
7. 7
   기타The organic layer was separated
8. 8
   세척washed with brine
9. 9
   건조dried over magnesium sulphate
10. 10
    기타evaporated to an orange oil
11. 11
    기타This was purified by column chromatography on silica using
12. 12
    온도increasing concentrations of methanol in dichloromethane as eluent

실험 절차

4-[3-({4-[(5-Chloro-7-iodo-1,3-benzodioxol-4-yl)amino]-6-methoxyquinazolin-7-yl}oxy)propyl]-1-methylpiperazin-2-one (250 mg, 0.40 mmol) and N,N-dimethyl-N′-prop-2-yn-1-ylurea (60 mg, 0.48 mmol) in ethyl acetate (8 ml) stirred at room temperature, under an atmosphere of nitrogen, and treated with bis(triphenylphosphine)palladium(II) dichloride (28 mg, 10 mol %) followed by copper(I) iodide (8 mg, 10 mol %) and diisopropylamine (81 mg, 0.80 mmol). The reaction was stirred 6 hr then DMF (3 ml) added and reaction heated at 60° for 3 hr. A further 60 mg N,N-dimethyl-N′-prop-2-yn-1-ylurea was added and heating continued for 3 hr. The mixture was then evaporated and the residue partitioned between water and dichloromethane. The organic layer was separated, washed with brine, dried over magnesium sulphate and evaporated to an orange oil. This was purified by column chromatography on silica using increasing concentrations of methanol in dichloromethane as eluent to give the title compound (164 mg, 66%) as a pale brown solid; NMR Spectrum:(DMSOd6) 1.99 (quintet, 2H), 2.54 (t, 2H), 2.66 (t, 2H), 2.81 (s, 9H), 3.00 (s, 2H), 3.28 (t, 2H), 3.93 (s, 3H), 4.10 (d, 2H), 4.20 (t, 2H), 6.14 (s, 2H), 6.82 (t, 1H), 7.07 (s, 1H), 7.23 (s(broad), 1H), 7.85 (s, 1H), 8.40 (s(br), 1H), 9.50 (s, 1H); Mass Spectrum: M+H+ 624/626.

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