Реакция #168365

Уравнение реакции

DIEA

sodium azide

iodomethane

3-(4-(5-chloropyridin-3-yl)-2-(2-ethynylpyrrolidin-1-yl)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridin-6-yl)-1,2,4-oxadiazol-5(4H)-one

→

3-(4-(5-chloropyridin-3-yl)-2-(2-(1-methyl-1H-1,2,3-triazol-4-yl)pyrrolidin-1-yl)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridin-6-yl)-1,2,4-oxadiazol-5(4H)-one

Растворители

DMSO

DMSO

Условия реакции

Обработка

1. 1
   ДругоеThe reaction vessel was sealed
2. 2
   ДругоеThe reaction vessel was sealed
3. 3
   workup.STIRRINGfurther stirred at 50° C. for 6 hours
4. 4
   Другоеthe solution was passed through a syringe
5. 5
   Фильтрацияfilter
6. 6
   ДругоеThe filtrate was purified by reverse phase preparative HPLC (0:100 to 95:5 acetonitrile:water: 0.1% v/v TFA modifier)

Методика

To a reaction vessel were added DMSO (0.4 mL), sodium azide (0.005 g, 0.080 mmol) and iodomethane (0.006 mL, 0.085 mmol). The reaction vessel was sealed and stirred at 50° C. for 12 hours. To the reaction was then added 3-(4-(5-chloropyridin-3-yl)-2-(2-ethynylpyrrolidin-1-yl)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridin-6-yl)-1,2,4-oxadiazol-5(4H)-one (0.020 g, 0.039 mmol), CuI (0.004 g, 0.019 mmol), and DIEA (0.015 mL, 0.086 mmol). The reaction vessel was sealed and further stirred at 50° C. for 6 hours. To the reaction was added DMSO (0.6 mL), and the solution was passed through a syringe filter. The filtrate was purified by reverse phase preparative HPLC (0:100 to 95:5 acetonitrile:water: 0.1% v/v TFA modifier) to afford 3-(4-(5-chloropyridin-3-yl)-2-(2-(1-methyl-1H-1,2,3-triazol-4-yl)pyrrolidin-1-yl)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridin-6-yl)-1,2,4-oxadiazol-5(4H)-one (TFA salt). MS ESI calc'd. for C28H31ClN10O2 [M+H]+ 575. found 575. 1H NMR (500 MHz, DMSO-d6): δ 12.81 (s, 1H); 8.85 (s, 1H); 8.77 (d, J=2.3 Hz, 1H); 8.41 (s, 1H); 7.94 (s, 1H); 7.79 (s, 1H); 5.50 (t, J=7.1 Hz, 1H); 3.94 (s, 3H); 3.80-3.86 (m, 3H); 3.43-3.46 (m, 1H); 2.37-2.39 (m, 1H); 2.12-2.18 (m, 2H); 1.95-2.00 (m, 1H); 1.28-1.30 (m, 2H); 0.96-1.03 (m, 2H); 0.66 (d, J=6.5 Hz, 4H); 0.41-0.44 (m, 3H); 0.30-0.36 (m, 2H).

Источник