Methyl iodide → 3-(2,5-Dichloropyrimidin-4-yl)-1-methyl-1H-indole

HRID 1842744Notes

Reaction equation

HRID 1842744 reaction equation
[H-].[Na+].[Cl:3][C:4]1[N:9]=[C:8]([C:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[NH:12][CH:11]=2)[C:7]([Cl:19])=[CH:6][N:5]=1.[CH3:20]I>C1COCC1.O>[Cl:3][C:4]1[N:9]=[C:8]([C:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[N:12]([CH3:20])[CH:11]=2)[C:7]([Cl:19])=[CH:6][N:5]=1

Participants

6

Reactant 3

HCID 6328Methyl iodide2×HCID 24758Sodium hydride2×HCID 566553763-(2,5-Dichloropyrimidin-4-yl)-1H-indole2×

Product 1

HCID 580714413-(2,5-Dichloropyrimidin-4-yl)-1-methyl-1H-indoleYield 70%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

NaH (0.795 g, 19.88 mmol) was added to 3-(2,5-dichloropyrimidin-4-yl)-1H-indole (Intermediate 11, 5.0 g, 18.9 mmol) in THF (200 mL) at 0° C. under N2 and the mixture was stirred at 0° C. for 0.25 h. CH3I (1.243 mL, 19.88 mmol) was then added and the mixture was allowed to warm to r.t. and was stirred for 1 h. The mixture was cooled again in an ice bath and further NaH (0.795 g, 19.88 mmol) was added. The suspension was stirred at 0° C. for 10 minutes then CH3I (1.243 mL, 19.88 mmol) was added and the mixture was stirred for 1 h. The mixture was then diluted with water (100 mL) which resulted in the formation of some solid. The solid was collected by filtration and was washed with water and EtOAc and then dried, to give the title compound (3.67 g, 70%) as a beige solid. The organic solution was further washed with water and sat. brine and then dried (MgSO4) and concentrated in vacuo. Trituration of the residue with diethyl ether gave a solid which was collected by filtration and dried in vacuo to give the title compound (477 mg, 9%) as a brown solid: This material was only 71% pure so it was kept separate from the earlier batch; 1H NMR: 3.97 (3H, s), 7.34 (2H, dtd), 7.59-7.65 (1H, m), 8.56 (1H, dd), 8.73 (1H, s), 8.79 (1H, s); m/z: ES+ MH+ 278.06.

Workup

  1. temperatureto warm to r.t.
  2. stirringwas stirred for 1 h
  3. temperatureThe mixture was cooled again in an ice bath
  4. stirringThe suspension was stirred at 0° C. for 10 minutes
  5. stirringthe mixture was stirred for 1 h
  6. customresulted in the formation of some solid
  7. filtrationThe solid was collected by filtration
  8. washwas washed with water and EtOAc
  9. customdried

Sources & evidence

ORD record
ord-fe3c877f5e2149f2bc9f6a62b610b266
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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