Water → 3-(4-Pyridinylamino)-1H-indole maleate

HRID 376870Notes

Reaction equation

HRID 376870 reaction equation
[NH2:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[NH:4][CH:3]=1.Cl.Cl[C:13]1[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=1.[OH2:19].[C:20](=[O:23])([O-:22])[O-].[Na+].[Na+].CN1C[CH2:30][CH2:29][C:28]1=[O:32]>>[C:28]([OH:32])(=[O:19])/[CH:29]=[CH:30]\[C:20]([OH:22])=[O:23].[N:16]1[CH:17]=[CH:18][C:13]([NH:1][C:2]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[NH:4][CH:3]=2)=[CH:14][CH:15]=1

Participants

6

Reactant 5

HCID 962WaterHCID 10340Sodium CarbonateHCID 13387N-methyl-2-pyrrolidoneHCID 818524-Chloropyridine hydrochloride2×HCID 2302801H-indol-3-amine

Product 1

HCID 700606793-(4-Pyridinylamino)-1H-indole maleate

Procedure

A solution of 3-aminoindole (8 g) and 4-chloropyridine hydrochloride (12 g) in 150 mL 1-methyl-2-pyrrolidinone (NMP hereinafter) was stirred at 70-75° C. for one hour, after which additional 4-chloropyridine hydrochloride (4 g) was added. After stirring a total of two hours, the mixture was cooled, stirred with water, basified with sodium carbonate and extracted with ethyl acetate. The organic extract was washed successively with water and a saturated sodium chloride solution and thereafter dried (anhydrous magnesium sulfate), filtered and concentrated to 20 g of a dark oil. This was eluted through silica with 20% methanol in dichloromethane (DCM hereinafter) via HPLC (high performance liquid chromatography) to yield 7 g of a dark oil. This oil was crystallized from acetonitrile to yield 3 g of light brown crystals, m.p. 192-193°. A 2.8 g portion was converted to the maleate salt in 50% methanol/ether to yield 3.5 g of light tan crystals, m.p. 149-151° C. Recrystallization from 50% methanol/ether yielded 3.4 g of light tan crystals, m.p. 149-151° C.

Workup

  1. temperaturethe mixture was cooled
  2. extractionextracted with ethyl acetate
  3. extractionThe organic extract
  4. washwas washed successively with water
  5. dry with materiala saturated sodium chloride solution and thereafter dried (anhydrous magnesium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated to 20 g of a dark oil
  8. washThis was eluted through silica with 20% methanol in dichloromethane (DCM hereinafter) via HPLC (high performance liquid chromatography)

Sources & evidence

ORD record
ord-f3fe3a9e09cc4014990b45129f2ebf23
Source dataset
uspto-grants-2000_02
Patent number
US06022880

Reaction notes

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