Potassium Carbonate → 1-(3-Fluoro-4-pyridinylamino)-5-phenylmethoxy-1H-indole

HRID 1029725Notes

Reaction equation

HRID 1029725 reaction equation
[C:1]1([CH2:7][O:8][C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[N:14]([NH2:18])[CH:13]=[CH:12]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.Cl[C:21]1[CH:26]=[CH:25][N:24]=[CH:23][C:22]=1[F:27].C([O-])([O-])=O.[K+].[K+]>CN1CCCC1=O>[F:27][C:22]1[CH:23]=[N:24][CH:25]=[CH:26][C:21]=1[NH:18][N:14]1[C:15]2[C:11](=[CH:10][C:9]([O:8][CH2:7][C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)=[CH:17][CH:16]=2)[CH:12]=[CH:13]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 149882975-(Benzyloxy)-1H-indol-1-amineHCID 193602344-Chloro-3-fluoropyridine hydrochloride

Product 1

HCID 199004641-(3-Fluoro-4-pyridinylamino)-5-phenylmethoxy-1H-indole

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
80 °C

Procedure

To 250 ml 1-methyl-2-pyrrolidinone was added 5-phenylmethoxy-1H-indol-1-amine (27.3 g), and the mixture was heated to 80° C. Then, 4-chloro-3-fluoropyridine hydrochloride (22 g) was added, and the mixture was heated at 80° C. for two hours. After cooling, the mixture was poured into 1 liter of ice-water, stirred for five minutes, and adjusted to pH 9 with milled K2CO3. The product was extracted with ethyl acetate (3×). The organic layer was washed with water (2×) and dried (saturated NaCl, anhydrous MgSO4). After filtration, the filtrate was concentrated to give an oil, 46 g of which was eluted on a silica gel column with ethyl acetate/dichloromethane (1:1) via HPLC. The desired fractions were combined and concentrated to give an oil, which solidified on cooling, 32.2 g, m.p. 140° C. A sample of this material was recrystallized from ether, m.p. 157°-159° C.

Workup

  1. temperaturethe mixture was heated at 80° C. for two hours
  2. temperatureAfter cooling
  3. extractionThe product was extracted with ethyl acetate (3×)
  4. washThe organic layer was washed with water (2×)
  5. dry with materialdried (saturated NaCl, anhydrous MgSO4)
  6. filtrationAfter filtration
  7. concentrationthe filtrate was concentrated
  8. customto give an oil, 46 g of which
  9. washwas eluted on a silica gel column with ethyl acetate/dichloromethane (1:1) via HPLC
  10. concentrationconcentrated
  11. customto give an oil, which
  12. temperatureon cooling
  13. customA sample of this material was recrystallized from ether, m.p. 157°-159° C.

Sources & evidence

ORD record
ord-1f0f3de137ad481888ba65f3fab713d8
Source dataset
uspto-grants-1992_04
Patent number
US05102891

Reaction notes

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