Triethylamine → N-(6-(2-Fluoro-4-nitrophenoxy)pyrimidin-4-yl)pyrrolidine-1-carboxamide

HRID 415907Notes

Reaction equation

HRID 415907 reaction equation
[F:1][C:2]1[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[CH:13]=[CH:12][C:3]=1[O:4][C:5]1[N:10]=[CH:9][N:8]=[C:7]([NH2:11])[CH:6]=1.[CH2:19]([N:21]([CH2:24][CH3:25])[CH2:22]C)[CH3:20].ClC(OC1C=CC=CC=1)=[O:28].N1CCCC1>O1CCCC1.[Cl-].[NH4+].ClCCl>[F:1][C:2]1[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[CH:13]=[CH:12][C:3]=1[O:4][C:5]1[N:10]=[CH:9][N:8]=[C:7]([NH:11][C:22]([N:21]2[CH2:24][CH2:25][CH2:20][CH2:19]2)=[O:28])[CH:6]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 31268PyrrolidineHCID 231530124-Amino-6-(2-fluoro-4-nitrophenoxy)pyrimidine

Product 1

HCID 57677447N-(6-(2-Fluoro-4-nitrophenoxy)pyrimidin-4-yl)pyrrolidine-1-carboxamideYield 43.2%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 25517Ammonium ChlorideSolvent

Procedure

6-(2-fluoro-4-nitrophenoxy)pyrimidin-4-amine (0.550 g, 2.2 mmol) was dissolved in tetrahydrofuran (10 ml). Then triethylamine (0.61 ml, 4.4 mmol) was added to the mixture with stirring. Then phenyl chloroformate (0.55 ml, 4.4 mmol) was added slowly to the mixture. The mixture was stirred at ambient temperature for 1.5 hours. Then pyrrolidine (1.8 ml, 22 mmol) was added to the mixture, and the mixture was stirred an additional 30 minutes. The mixture was diluted with sat. ammonium chloride and dichloromethane and stirred an additional 10 minutes. The organic layer was collected by extracting with dichloromethane (3×10 ml). Combined organic layer was dried over sodium sulfate, filtered, and concentrated in-vacuo. The crude was purified by chromatography (Amino-Propyl silica gel column) in a gradient of 1-5% MeOH/dichloromethane to give an oil. The oil was recrystallized from dichloromethane/hexanes to give the desired product N-(6-(2-fluoro-4-nitrophenoxy)pyrimidin-4-yl)pyrrolidine-1-carboxamide (0.330 g, 0.95 mmol, 43% yield) as a yellow solid. MS (ESI pos. ion) m/z: 348 (MH+). Calc'd exact mass for C15H14FN5O4: 347. 1NMR (300 MHz, CDCl3): 1.94 (s, 4H), 3.37-3.49 (m, 4H), 5.23 (s, 1H), 7.09-7.21 (m, 1H), 7.29-7.38 (m, 1H), 7.99-8.09 (m, 2H), 8.25 (d, J=0.73 Hz, 1H).

Workup

  1. stirringThe mixture was stirred at ambient temperature for 1.5 hours
  2. stirringthe mixture was stirred an additional 30 minutes
  3. stirringstirred an additional 10 minutes
  4. customThe organic layer was collected
  5. extractionby extracting with dichloromethane (3×10 ml)
  6. dry with materialCombined organic layer was dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in-vacuo
  9. customThe crude was purified by chromatography (Amino-Propyl silica gel column) in a gradient of 1-5% MeOH/dichloromethane
  10. customto give an oil
  11. customThe oil was recrystallized from dichloromethane/hexanes

Sources & evidence

ORD record
ord-373b9ca69cf54013b38a23276cbfbe86
Source dataset
uspto-grants-2012_01
Patent number
US08088794B2

Reaction notes

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