Acetic Acid → 3-(2,5-Dichloropyrimidin-4-yl)-1H-indole

Temperature

1 °C

CH3MgBr (3.2M in 2-methyltetrahydrofuran, 3.37 mL, 10.79 mmol) was added dropwise over 10 minutes to a solution of indole (1.28 g, 10.79 mmol) in THF (6 mL) at 0° C. The solution was then stirred at 0-2° C. for 0.5 h. 2,4,5-Trichloropyrimidine (1 g, 5.40 mmol) was then added dropwise, resulting in a yellow solution. The ice bath was removed, then the solution was stirred at r.t. for 1 h, resulting in a red solution. The mixture was heated to 60° C. and then stirred at 60° C. for 1.5 h. The mixture was then cooled to r.t. and acetic acid (634 μL, 11.06 mmol) was added dropwise. Water (9.90 mL) and THF (2 mL) were added, then the mixture was stirred for 20 minutes at 60° C., resulting in a bi-phasic solution. The layers were separated and heptane (11 mL) was added to the organic solution, resulting in the crystallisation of a solid. The solid was collected by filtration, washed with heptane (2 mL), and dried in a vacuum oven to give the title compound (1.015 g, 66%) as a yellow solid; 1H NMR: 7.24-7.32 (2H, m), 7.55-7.58 (1H, m), 8.52-8.55 (1H, m), 8.71-8.73 (2H, m), 12.24 (1H, s); m/z: ES+ MH+ 264, 266.

1. customresulting in a yellow solution
2. customThe ice bath was removed
3. stirringthe solution was stirred at r.t. for 1 h
4. customresulting in a red solution
5. temperatureThe mixture was heated to 60° C.
6. stirringstirred at 60° C. for 1.5 h
7. temperatureThe mixture was then cooled to r.t.
8. stirringthe mixture was stirred for 20 minutes at 60° C.
9. customresulting in a bi-phasic solution
10. customThe layers were separated
11. additionheptane (11 mL) was added to the organic solution
12. customresulting in the crystallisation of a solid
13. filtrationThe solid was collected by filtration
14. washwashed with heptane (2 mL)
15. customdried in a vacuum oven

ORD record

ord-24c38189a71e442ba8909c9e784bceff

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08946235B2