تفاعل #976638

معادلة التفاعل

5B

6-chloro-8-((5-methoxypyridin-2-yl)(4-methoxybenzyl)amino)imidazo[1,2-b]pyridazine-3-carbonitrile

N-(5-amino-2-methylphenyl)acetamide

Xantphos

Cs2CO3

→

5C

المردود 61.8%

N-(5-(3-cyano-8-((5-methoxypyridin-2-yl)(4-methoxybenzyl)amino)imidazo[1,2-b]pyridazin-6-ylamino)-2-methylphenyl)acetamide

المردود 61.8%

المذيبات

DMA

ظروف التفاعل

المعالجة

1. 1
   أخرىwas purged with nitrogen
2. 2
   workup.ADDITIONthe reaction mixture was diluted with ethyl acetate
3. 3
   غسيلwashed with 15% NH4OH
4. 4
   تجفيفdried over Na2SO4
5. 5
   تركيزconcentrated to dryness under reduced pressure
6. 6
   أخرىThe resulting oil was purified by silica column chromatography (gradient=0%-100% hexanes to ethyl acetate in 12 min.)

الإجراء التجريبي

A mixture of 5B (60 mg, 0.14 mmol), N-(5-amino-2-methylphenyl)acetamide (46.8 mg, 0.29 mmol), Pd2(dba)3 (13.1 mg, 0.014 mmol), Xantphos (18.2 mg, 0.031 mmol), copper(I) iodide (13.6 mg, 0.071 mmol) and Cs2CO3 (186 mg, 0.57 mmol) in DMA (1 mL) was purged with nitrogen and heated at 125° C. After 1.5 hours, the reaction mixture was diluted with ethyl acetate, washed with 15% NH4OH, dried over Na2SO4, and concentrated to dryness under reduced pressure. The resulting oil was purified by silica column chromatography (gradient=0%-100% hexanes to ethyl acetate in 12 min.) to isolate 5C (47.5 mg, 60.7% yield). HPLC: Rt=3.805 min (YMC S5 ODS 4.6×50 mm, 10-90% aqueous methanol containing 0.2% H3PO4, 4 min gradient, monitored at 220 nm). MS (ES): m/z=549.2 [M+H]+.

المصدر