تفاعل #1872320

معادلة التفاعل

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

المردود 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

المردود 66.0%

المذيبات

ethyl acetate

ظروف التفاعل

المعالجة

1. 1
   أخرىreaction
2. 2
   درجة الحرارةheated at 60° for 3 hr
3. 3
   درجة الحرارةheating
4. 4
   workup.WAITcontinued for 3 hr
5. 5
   أخرىThe mixture was then evaporated
6. 6
   أخرىthe residue partitioned between water and dichloromethane
7. 7
   أخرىThe organic layer was separated
8. 8
   غسيلwashed with brine
9. 9
   تجفيفdried over magnesium sulphate
10. 10
    أخرىevaporated to an orange oil
11. 11
    أخرىThis was purified by column chromatography on silica using
12. 12
    درجة الحرارةincreasing concentrations of methanol in dichloromethane as eluent

الإجراء التجريبي

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.

المصدر