تفاعل #68626

معادلة التفاعل

diisopropylethylamine

2,2-difluoro-N′-(3-fluoro-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-2-(3-methoxyquinolin-6-yl)acetohydrazide

triphenylphosphine

2,2,2-trichloroacetonitrile

dichloroethane

→

6-(difluoro(8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)-3-methoxyquinoline

المردود 44.0%

المذيبات

MeOH

ظروف التفاعل

المعالجة

1. 1
   أخرىThe flask was sealed
2. 2
   أخرىThe resulting mixture was irradiated in a microwave (Biotage Initiator) at 150° C. for 40 min
3. 3
   ترشيحThe reaction mixture was filtered
4. 4
   غسيلthe filter cake was washed with CH2Cl2 (15 mL) and MeOH (10 mL)
5. 5
   تركيزThe filtrate was concentrated in vacuo
6. 6
   أخرىthe resulting crude residue was purified by MPLC

الإجراء التجريبي

A sealable microwave vial was charged with 2,2-difluoro-N′-(3-fluoro-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-2-(3-methoxyquinolin-6-yl)acetohydrazide (225 mg, 509 μmol) and polymer supported triphenylphosphine (2.3 mmol/g, 221 mg, 509 μmol). The flask was sealed and dichloroethane (4 mL) was added followed by diisopropylethylamine (89 μl, 509 μmol) and 2,2,2-trichloroacetonitrile (127 μl, 1271 μmol). The resulting mixture was irradiated in a microwave (Biotage Initiator) at 150° C. for 40 min. The reaction mixture was filtered and the filter cake was washed with CH2Cl2 (15 mL) and MeOH (10 mL). The filtrate was concentrated in vacuo and the resulting crude residue was purified by MPLC using 100% CH2Cl2 to 98:2 CH2Cl2: MeOH to afford 6-(difluoro(8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)-3-methoxyquinoline (94 mg, 44% yield) as a tan amorphous solid. LRMS (ESI) m/z calcd for C21H16F3N6O (M+H) 425.1. found 425.4.

المصدر