Acetic Acid → 3-(2-Chloro-5-methylpyrimidin-4-yl)-1H-indole

HRID 1842684Notes

Reaction equation

C[Mg+].[Br-].[NH:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]=[CH:5]1.[Cl:13][C:14]1[N:19]=[C:18](Cl)[C:17]([CH3:21])=[CH:16][N:15]=1.C(O)(=O)C>C1COCC1.O>[Cl:13][C:14]1[N:19]=[C:18]([C:6]2[C:7]3[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=3)[NH:4][CH:5]=2)[C:17]([CH3:21])=[CH:16][N:15]=1

Participants

Conditions

Temperature: 1 °C

Procedure

CH3MgBr (3.2M in 2-methyltetrahydrofuran, 3.76 mL, 12.02 mmol) was added dropwise over 10 minutes to a solution of indole (1.42 g, 12.02 mmol) in THF (4.9 mL) at 0° C. The solution was then stirred at 0-2° C. for 0.5 h. A solution of 2,4-dichloro-5-methylpyrimidine (1 g, 6.01 mmol) in THF (3 mL) was then added dropwise to the solution. The ice bath was then removed, then the solution was stirred at r.t. for 1 h then 60° C. for 21 h. While still at 60° C., acetic acid (708 μL, 12.32 mmoles) was added dropwise, followed by water (10 mL). The resulting biphasic suspension was stirred at 60° C. for 0.5 h. The resulting solid was collected by filtration, washed with water (5 mL), and dried in a vacuum oven to give the title compound (805 mg, 50%) as a white solid; 1H NMR: 2.49 (3H, s), 7.20-7.28 (2H, m), 7.52-7.55 (1H, m), 8.20 (1H, d), 8.48 (1H, d), 8.51-8.54 (1H, m), 12.10 (1H, s); m/z: ES+ MH+ 244.

Workup

customThe ice bath was then removed
stirringthe solution was stirred at r.t. for 1 h
wait60° C. for 21 h
stirringThe resulting biphasic suspension was stirred at 60° C. for 0.5 h
filtrationThe resulting solid was collected by filtration
washwashed with water (5 mL)
customdried in a vacuum oven

Sources & evidence

ORD record: ord-149d13286316452ba08b0cf1a3d6562d
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08946235B2

Reaction notes

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