تفاعل #490112

معادلة التفاعل

8-bromo-6-chloroimidazo[1,2-b]pyridazine

5-(4-isopropylpiperazin-1-yl)pyridin-2-amine

sodium hydride

→

(6-chloro-imidazo[1,2-b]pyridazin-8-yl)-[5-(4-isopropyl-piperazin-1-yl)-pyridin-2-yl]-amine

المردود 24.3%

المذيبات

DMF

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةto warm to room temperature
2. 2
   workup.STIRRINGstir 18 h
3. 3
   أخرىThe reaction mixture was quenched with sat. NaHCO3 (aq)
4. 4
   workup.ADDITIONdiluted with water and EtOAc
5. 5
   أخرىThe organic layer was separated
6. 6
   استخلاصthe aqueous phase was extracted with EtOAc
7. 7
   تجفيفdried over MgSO4
8. 8
   تركيزconcentrated in vacuo
9. 9
   أخرىThe crude material was purified by flash chromatography (silica gel, 0% to 20% (60:10:1 DCM:MeOH:NH4OH)/DCM gradient)
10. 10
    أخرىto give a residue that
11. 11
    workup.WAITwas placed under high vacuum for 18 h

الإجراء التجريبي

A mixture of 8-bromo-6-chloroimidazo[1,2-b]pyridazine (200 mg, 862 μmol, Eq: 0.95) and 5-(4-isopropylpiperazin-1-yl)pyridin-2-amine (200 mg, 908 μmol, Eq: 1.00) in DMF (10.0 ml) was cooled to 0° C. To this reaction mixture was added sodium hydride (116 mg, (60% in mineral oil), 2.9 mmol, Eq: 3.2). The reaction was allowed to stir at 0° C. for 10 min then allowed to warm to room temperature and stir 18 h. The reaction mixture was quenched with sat. NaHCO3 (aq) and diluted with water and EtOAc. The organic layer was separated and the aqueous phase was extracted with EtOAc. The organic layers were combined, dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 0% to 20% (60:10:1 DCM:MeOH:NH4OH)/DCM gradient) to give a residue that was placed under high vacuum for 18 h to afford (6-chloro-imidazo[1,2-b]pyridazin-8-yl)-[5-(4-isopropyl-piperazin-1-yl)-pyridin-2-yl]-amine (78 mg, 23%). LC/MS-ESI observed [M+H]+ 372.

المصدر