Реакция #68628

Уравнение реакции

Di-tert-butyl azodicarboxylate

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

triphenylphosphine

4-(3-hydroxypropyl)-morpholine

→

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

Выход 33.0%

Растворители

MeOH

CH2Cl2

MeOH

THF

Условия реакции

Обработка

1. 1
   Температураto warm to rt
2. 2
   Температураwas maintained for 48 h
3. 3
   КонцентрированиеThe solution was concentrated for purification by MPLC (Teledine Isco combiFlash Companion)
4. 4
   Другоеabsorbed onto a 5 g loading cartridge

Методика

To a flask charged with 6-(difluoro(8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)quinolin-3-ol (17.3 mg, 42 μmol), was added triphenylphosphine (55 mg, 211 μmol), THF (1 mL), and 4-(3-hydroxypropyl)-morpholine, 95% (31 μl, 211 μmol). The mixture was placed under N2 and cooled to 0° C. Di-tert-butyl azodicarboxylate (49 mg, 211 μmol) was added as a solid in a single portion and the solution was allowed to warm to rt and was maintained for 48 h. The solution was concentrated for purification by MPLC (Teledine Isco combiFlash Companion). The crude residue was taken up in minimal CH2Cl2 and absorbed onto a 5 g loading cartridge and passed through a Redi-Sep® pre-packed silica gel column (40 g) using 99:1 CH2Cl2: MeOH to 90:10 CH2Cl2: MeOH gradient 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-(3-morpholinopropoxy)quinoline (7.5 mg, 33% yield) as a colorless solid. LRMS (ESI) m/z calcd for C27H27F3N7O2 (M+H) 538.2. found 538.2.

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