반응 #1872332

반응 방정식

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

수율 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

수율 85.0%

용매

ethyl acetate

반응 조건

후처리

1. 1
   workup.STIRRINGthe reaction stirred for a further 1 hr
2. 2
   기타The resulting orange solution was evaporated in vacuo
3. 3
   workup.ADDITIONthen treated with dilute aqueous sodium bicarbonate solution
4. 4
   추출extracted with dichloromethane
5. 5
   건조The extract was dried over magnesium sulphate
6. 6
   기타evaporated to an orange oil
7. 7
   기타Purification
8. 8
   온도increasing concentrations of methanolic ammonia in dichloromethane as eluent

실험 절차

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;

출처