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

HRID 5891

Reaction equation

HRID 5891 reaction equation
Cl.Cl[C:3]1[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=1.[NH2:9][C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[N:15]([CH3:19])[CH:14]=[CH:13]2.O.C(=O)([O-])[O-].[Na+].[Na+]>CN1CCCC1=O>[CH3:19][N:15]1[C:16]2[C:12](=[CH:11][C:10]([NH:9][C:3]3[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=3)=[CH:18][CH:17]=2)[CH:13]=[CH:14]1

Participants

6

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 818524-Chloropyridine hydrochloride2×HCID 27695641-methyl-1H-indol-5-amine

Product 1

HCID 98159221-Methyl-5-(4-pyridinylamino)-1H-indoleYield 53.3%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

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.

Workup

  1. custompreheated to 100° C
  2. customno further reaction
  3. temperatureAfter two hours the reaction mixture was cooled
  4. extractionextracted with ethyl acetate
  5. dry with materialThe dried (anhydrous magnesium sulfate) organic layer
  6. filtrationwas filtered
  7. customevaporated to 12.7 g of an oil
  8. washThe oil was eluted through silica with 10% methanol in dichloromethane via flash column chromatography
  9. customto give the product which
  10. customwas triturated with ether

Sources & evidence

ORD record
ord-5f7c51d628ad4fcda89d3d4a2d4eafae
Source dataset
uspto-grants-1993_09
Patent number
US05246947

Linked notes

Loading…