Ammonium Chloride → 4-(4-Amino-2-fluorophenoxy)-2-[(pyrrolidin-1-yl)carbonylamino]pyridine

HRID 2359696Notes

Reaction equation

HRID 2359696 reaction equation
[F:1][C:2]1[CH:22]=[C:21]([N+:23]([O-])=O)[CH:20]=[CH:19][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]([NH:11][C:12]([N:14]2[CH2:18][CH2:17][CH2:16][CH2:15]2)=[O:13])[CH:6]=1.[Cl-].[NH4+]>C(O)C.O.[Fe]>[NH2:23][C:21]1[CH:20]=[CH:19][C:3]([O:4][C:5]2[CH:10]=[CH:9][N:8]=[C:7]([NH:11][C:12]([N:14]3[CH2:15][CH2:16][CH2:17][CH2:18]3)=[O:13])[CH:6]=2)=[C:2]([F:1])[CH:22]=1

Participants

5

Reactant 2

HCID 25517Ammonium ChlorideHCID 231530114-(2-Fluoro-4-nitrophenoxy)-2-[(pyrrolidin-1-yl)carbonylamino]pyridine

Product 1

HCID 231530584-(4-Amino-2-fluorophenoxy)-2-[(pyrrolidin-1-yl)carbonylamino]pyridineYield 76.9%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 19096565Water ethanolSolvent

Procedure

N-(4-(2-fluoro-4-nitrophenoxy)pyridin-2-yl)pyrrolidine-1-carboxamide (0.180 g, 0.52 mmol) was dissolved in a mixture of 3:1 ethanol/water (4 ml) with stirring. Then iron (0.160 g, 2.8 mmol) and ammonium chloride (0.016 g, 0.30 mmol) was added to the mixture. The mixture was placed in a pre-heated oil-bath (80° C.) for 1 hour. The oil bath was removed, and the mixture was allowed to cool to ambient temperature. The mixture was filtered through filter diskette. The flask was rinsed with methanol (3×10 ml), and the combined filtrate was evaporated in-vacuo. The residue was diluted with dichloromethane and 1N NaOH (2 ml). The organic were extracted with dichloromethane (3×10 ml), dried over sodium sulfate, filtered and concentrated in vacuo. to give the desired product N-(4-(4-amino-2-fluorophenoxy)pyridin-2-yl)pyrrolidine-1-carboxamide (0.125 g, 0.4 mmol, 76% yield) as a tan oil. MS (ESI pos. ion) m/z: 317 (MH+). Calc'd exact mass for C16H17FN4O2: 316. 1HNMR (300 MHz, CDCl3): 1.96 (s, 4H), 3.44 (s, 4H), 6.52 (d, J=3.07 Hz, 2H), 6.96 (s, 1H), 7.26 (s, 1H), 7.67 (s, 1H), 8.01 (d, J=5.70 Hz, 1H).

Workup

  1. customThe mixture was placed in a pre-heated oil-bath
  2. customThe oil bath was removed
  3. filtrationThe mixture was filtered
  4. filtrationthrough filter diskette
  5. washThe flask was rinsed with methanol (3×10 ml)
  6. customthe combined filtrate was evaporated in-vacuo
  7. additionThe residue was diluted with dichloromethane and 1N NaOH (2 ml)
  8. extractionThe organic were extracted with dichloromethane (3×10 ml)
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c7c5d51796bb4f69988303b9f6417561
Source dataset
uspto-grants-2014_04
Patent number
US08685983B2

Reaction notes

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