Ammonium Chloride → 4-(4-Amino-2-fluorophenoxy)-6-[(pyrrolidin-1-yl)carbonylamino]pyrimidine

HRID 415908Notes

Reaction equation

HRID 415908 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[N: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[N:10]=[CH:9][N:8]=[C:7]([NH:11][C:12]([N:14]3[CH2:18][CH2:17][CH2:16][CH2:15]3)=[O:13])[CH:6]=2)=[C:2]([F:1])[CH:22]=1

Participants

5

Reactant 2

HCID 25517Ammonium ChlorideHCID 57677447N-(6-(2-Fluoro-4-nitrophenoxy)pyrimidin-4-yl)pyrrolidine-1-carboxamide

Product 1

HCID 231534594-(4-Amino-2-fluorophenoxy)-6-[(pyrrolidin-1-yl)carbonylamino]pyrimidineYield 82.1%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 19096565Water ethanolSolvent

Procedure

N-(6-(2-fluoro-4-nitrophenoxy)pyrimidin-4-yl)pyrrolidine-1-carboxamide (0.320 g, 0.921 mmol) was dissolved in a mixture of 3:1 ethanol/water (8 ml). Then iron (0.276 g, 4.95 mmol) and ammonium chloride (0.0281 g, 0.525 mmol) was added to the mixture with stirring. The mixture was placed in a pre-heated oil bath (80° C.) for 1 hour. The oil bath was removed to allow the mixture to cool to ambient temperature. The mixture was filtered through a filter diskette. The flask was rinsed with methanol (3×10 ml) and filtered through diskette. Combined organic solution was concentrated in-vacuo. Then water was added to the mixture with stirring. The precipitate was collected by filtration and washed with hexanes. The solid was dried in a reduced-pressure oven to give the desired product N-(6-(4-amino-2-fluorophenoxy)pyrimidin-4-yl)pyrrolidine-1-carboxamide (0.240 g, 0.756 mmol, 82% yield) as a yellow solid. MS (ESI pos. ion) m/z: 318 (MH+). Calc'd exact mass for C15H16FN5O2: 317. 1HNMR (300 MHz, CDCl3): 1.91-2.05 (s, 4H), 3.41-3.54 (t, 4H), 6.41-6.52 (m, 2H), 6.92-7.01 (t, 1H), 7.21 (s, 1H), 7.63 (s, 1H), 8.36 (s, 1H).

Workup

  1. customThe mixture was placed in a pre-heated oil bath
  2. customThe oil bath was removed
  3. filtrationThe mixture was filtered through a filter diskette
  4. washThe flask was rinsed with methanol (3×10 ml)
  5. filtrationfiltered through diskette
  6. concentrationCombined organic solution was concentrated in-vacuo
  7. additionThen water was added to the mixture
  8. stirringwith stirring
  9. filtrationThe precipitate was collected by filtration
  10. washwashed with hexanes
  11. customThe solid was dried in a reduced-pressure oven

Sources & evidence

ORD record
ord-2bb909478d9442bdb2ab52c1b82f275a
Source dataset
uspto-grants-2012_01
Patent number
US08088794B2

Reaction notes

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