تفاعل #1872332

معادلة التفاعل

N-(5-Chloro-7-iodo-1,3-benzodioxol-4-yl)-7-[3-(cis-2,6-dimethylmorpholin-4-yl)propoxy]-6-methoxyquinazolin-4-amine

N,N-dimethyl-N′-prop-2-yn-1-ylurea

DMF

→

title compound

المردود 85.0%

N′-{3-[6-Chloro-7-({7-[3-(cis-2,6-dimethylmorpholin-4-yl)propoxy]-6-methoxyquinazolin-4-yl}amino)-1,3-benzodioxol-4-yl]prop-2-yn-1-yl}-N,N-dimethylurea

المردود 85.0%

المذيبات

ethyl acetate

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGthe reaction stirred for a further 1 hr
2. 2
   أخرىThe resulting orange solution was evaporated in vacuo
3. 3
   workup.ADDITIONthen treated with dilute aqueous sodium bicarbonate solution
4. 4
   استخلاصextracted with dichloromethane
5. 5
   تجفيفThe extract was dried over magnesium sulphate
6. 6
   أخرىevaporated to an orange oil
7. 7
   أخرىPurification
8. 8
   درجة الحرارةincreasing concentrations of methanolic ammonia in dichloromethane as eluent

الإجراء التجريبي

N-(5-Chloro-7-iodo-1,3-benzodioxol-4-yl)-7-[3-(cis-2,6-dimethylmorpholin-4-yl)propoxy]-6-methoxyquinazolin-4-amine (250 mg, 0.40 mmol) and N,N-dimethyl-N′-prop-2-yn-1-ylurea (100 mg, 0.79 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 diisopropylamnine (81 mg, 0.81 mmol). The reaction was stirred 1 hr then DMF (4 ml) added and the reaction stirred for a further 1 hr. The resulting orange solution was evaporated in vacuo then treated with dilute aqueous sodium bicarbonate solution and extracted with dichloromethane. The extract was dried over magnesium sulphate and evaporated to an orange oil. Purification was by column chromatography on silica using increasing concentrations of methanolic ammonia in dichloromethane as eluent gave the title compound (211 mg, 85%) as a pale orange solid;

المصدر