ChemicalBook CAS DataBase List 3-(2-chloropyriMidin-4-yl)-1-Methylindole

3-(2-chloropyriMidin-4-yl)-1-Methylindole synthesis

7synthesis methods

Product Name:3-(2-chloropyriMidin-4-yl)-1-Methylindole
CAS Number:1032452-86-0
Molecular formula:C13H10ClN3
Molecular Weight:243.69

3934-20-1

603-76-9

1032452-86-0

The general procedure for the synthesis of 3-(2-chloropyrimidin-4-yl)-1-methylindole from 2,4-dichloropyrimidine and N-methylindole is as follows: Intermediate 7: Synthesis of 3-(2-chloropyrimidin-4-yl)-1-methylindole 40g of 2,4-dichloropyrimidine and 200mL of 1,2-dimethoxyethane (DME) were added to a 1L three-neck flask and stirred until complete dissolution. After cooling the reaction system to 10-15°C, 45 g of anhydrous ferric chloride (FeCl3) was added rapidly and in batches, controlling the reaction temperature to not exceed 35°C. Stirring of the reaction mixture was continued for 15 minutes after each portion of FeCl3 was added. Subsequently, 52.8 g of N-methylindole was slowly added dropwise to the reaction system. After the dropwise addition, the reaction mixture was slowly heated to 50°C and stirred at this temperature overnight. The progress of the reaction was monitored by thin layer chromatography (TLC) until the reaction was completed. Upon completion of the reaction, the mixture was cooled to 5-10°C and about 300 mL of a mixture of methanol and water (1:2 by volume) was slowly added dropwise, at which time a large amount of viscous solid precipitated. The reaction mixture was filtered, the solid product was collected and the filter cake was washed twice with methanol. Finally, the resulting solid was dried under reduced pressure at 50°C to give the target product in 85% yield.

945016-63-7 Synthesis

945016-63-7
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74-88-4
356 suppliers
$15.00/10g

1032452-86-0
306 suppliers
$9.00/1g

Yield:1032452-86-0 96%

Reaction Conditions:

Stage #1: 3-(2-chloro-pyrimidin-4-yl)-1H-indolewith sodium hydride in tetrahydrofuran;mineral oil at 0; for 0.5 h;
Stage #2: methyl iodide in tetrahydrofuran;mineral oil at 0; for 3 h;

Steps:

130 Intermediate 130: 3-(2-Chloropyrimidin-4-yl)-1-methylindole

NaH (1.707 g, 42.68 mmol, 40% dispersion in mineral oil) was added in small portions to a cooled (0°C) mixture of 3-(2-chloropyrimidin-4-yl)-1H-indole (Intermediate 131, 8.168 g, 35.57 mmol) in THF (250 mL). The resulting mixture was stirred at 0°C for 0.5h and then CH₃I (2.67 mL, 42.68 mmol) was added and the mixture stirred at 0°C for a further 3h. The reaction was quenched by the addition of sat. NaHCO₃ (25 mL). The mixture was then diluted with EtOAc (100 mL), and the resulting solution was washed with sat. NaHCO₃ (50 mL), water (50 mL) and sat. brine (50 mL). The organic solution was then concentrated in vacuo. Purification by FCC, eluting with 0-20% CH₃OH in CH₂Cl₂ gave the title compound (8.35 g, 96%) as a pale yellow solid; ¹H NMR: 3.90 (3H, s), 7.30 (2H, pd), 7.54-7.60 (1H, m), 7.82 (1H, d), 8.38-8.44 (1H, m), 8.49 (1H, s), 8.53 (1H, d); m/z: ES⁺ MH⁺ 244.

References:

WO2013/14448,2013,A1 Location in patent:Page/Page column 138

3934-20-1 Synthesis

3934-20-1
736 suppliers
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603-76-9
438 suppliers
$18.00/5g

1032452-86-0
306 suppliers
$9.00/1g

References

945016-63-7 Synthesis

945016-63-7
86 suppliers
$44.00/100mg

50-00-0 Synthesis