تفاعل #366759

معادلة التفاعل

2-(N-(2,6-dimethyl-4-pyridyl)-N-methylamino)ethanol

aluminium oxide

Diethyl azodicarboxylate

4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline

triphenylphosphine

→

4-(4-chloro-2-fluoroanilino)-7-(2-(N-(2,6-dimethyl-4-pyridyl)-N-methylamino)ethoxy)-6-methoxyquinazoline

المردود 70.5%

المذيبات

methylene chloride

ظروف التفاعل

المعالجة

1. 1
   أخرى(prepared
2. 2
   أخرىthe product was separated by elution with methylene chloride/acetonitrile/methanol (60/35/35)
3. 3
   أخرىThe purified solid product was triturated with ether
4. 4
   ترشيحcollected by filtration
5. 5
   workup.DISSOLUTIONThe solid was dissolved in methylene chloride/methanol
6. 6
   workup.ADDITIONa solution of 3M ethereal hydrogen chloride (1 ml) was added
7. 7
   ترشيحThe solid was collected by filtration
8. 8
   غسيلwashed with ether
9. 9
   أخرىdried under vacuum

الإجراء التجريبي

Diethyl azodicarboxylate (261 mg, 1.5 mmol) was added dropwise to a suspension of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (160 mg, 0.5 mmol), (prepared as described for the starting material in Example 24), triphenylphosphine (393 mg, 1.5 mmol) and 2-(N-(2,6-dimethyl-4-pyridyl)-N-methylamino)ethanol (125 mg, 0.7 mmol) in methylene chloride (5 ml) and the mixture stirred for 2 hours at ambient temperature. Methanol (10 drops) was added and the mixture was poured on to a column of neutral aluminium oxide and the product was separated by elution with methylene chloride/acetonitrile/methanol (60/35/35). The purified solid product was triturated with ether and collected by filtration. The solid was dissolved in methylene chloride/methanol and a solution of 3M ethereal hydrogen chloride (1 ml) was added. The solid was collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-7-(2-(N-(2,6-dimethyl-4-pyridyl)-N-methylamino)ethoxy)-6-methoxyquinazoline (170 mg, 61%).

المصدر