Acetonitrile → 5-((2-chloropyrimidin-4-yl)oxy)-2-methyl-1H-indole

HRID 244520Notes

Reaction equation

[OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([CH3:11])=[CH:5]2.C(#N)C.C(=O)([O-])[O-].[K+].[K+].[Cl:21][C:22]1[N:27]=[C:26](Cl)[CH:25]=[CH:24][N:23]=1>O>[Cl:21][C:22]1[N:27]=[C:26]([O:1][C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[NH:7][C:6]([CH3:11])=[CH:5]3)[CH:25]=[CH:24][N:23]=1

Participants

Conditions

Temperature: 2.5 °C

Procedure

To a 50 L three-neck round bottom flask, equipped with a mechanical stirrer, addition funnel and thermometer, were added 2-methyl-1H-indol-5-ol (compound 1, 3 Kg), anhydrous acetonitrile (9 L) and potassium carbonate (4.2 Kg). The reaction mixture was cooled to 0-5° C. with stirring under N2. A solution of 2,4-dichloropyrimidine (Compound 2, 3.05 Kg, in 9 L of acetonitrile) was added to the reaction mixture dropwise while keeping the inner temperature of the reaction in the range from 0 to 5° C. After addition was complete, the reaction mixture was allowed to warm to a temperature ranging from 5 to 10° C. over a period of 4-8 hours. When reaction was completed, the reaction mixture was poured into 54 L of distilled water in a 100 L reactor with stirring, and stirred for another hour at room temperature. The precipitates were collected by filtration and the filter cake was washed with pure water to afford Compound 3 (5.7 Kg).

Workup

customTo a 50 L three-neck round bottom flask, equipped with a mechanical stirrer, addition funnel
customthe inner temperature of the reaction in the range from 0 to 5° C
additionAfter addition
temperatureto warm to a temperature
customWhen reaction
stirringwith stirring
stirringstirred for another hour at room temperature
filtrationThe precipitates were collected by filtration
washthe filter cake was washed with pure water

Sources & evidence

ORD record: ord-578e6c35cd844160b63a31cb00a95420
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08658658B2

Reaction notes

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