Reaction #5987

Reaction equation

water

4-Chloropyridine hydrochloride

5-amino-1-methylindole

sodium carbonate

4-chloropyridine hydrochloride

→

solid

Yield 53.3%

1-Methyl-5-(4-pyridinylamino)-1H-indole

Yield 53.3%

Solvents

1-methyl-2-pyrrolidinone

Conditions

Workup

1. 1
   Otherpreheated to 100° C
2. 2
   Otherno further reaction
3. 3
   TemperatureAfter two hours the reaction mixture was cooled
4. 4
   Extractionextracted with ethyl acetate
5. 5
   DryingThe dried (anhydrous magnesium sulfate) organic layer
6. 6
   Filtrationwas filtered
7. 7
   Otherevaporated to 12.7 g of an oil
8. 8
   WashThe oil was eluted through silica with 10% methanol in dichloromethane via flash column chromatography
9. 9
   Otherto give the product which
10. 10
    Otherwas triturated with ether

Procedure

4-Chloropyridine hydrochloride (8 g) was added to a solution of 5-amino-1-methylindole (7 g) in 75 ml 1-methyl-2-pyrrolidinone preheated to 100° C. The addition of 4-chloropyridine hydrochloride (4 g) after one hour caused no further reaction as determined by TLC. After two hours the reaction mixture was cooled, stirred with water, basified with sodium carbonate and extracted with ethyl acetate. The dried (anhydrous magnesium sulfate) organic layer was filtered and evaporated to 12.7 g of an oil. The oil was eluted through silica with 10% methanol in dichloromethane via flash column chromatography to give the product which was triturated with ether to yield 5.7 g of a solid, m.p. 202°-203° C. Recrystallization from acetonitrile yielded 5 g of product as crystals, mp 209°-211° C.

Source