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

HRID 492720Notes

Reaction equation

HRID 492720 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][C:10]=2[F:18])[N:5]=[CH:4][N:3]=1.[CH2:19]([N:21]([CH2:24][CH3:25])[CH2:22]C)[CH3:20].ClC(OC1C=CC=CC=1)=[O:28].N1CCCC1>O1CCCC1>[F:18][C:10]1[CH:11]=[C:12]([N+:15]([O-:17])=[O:16])[CH:13]=[CH:14][C:9]=1[O:8][C:6]1[N:5]=[CH:4][N:3]=[C:2]([NH:1][C:22]([N:21]2[CH2:24][CH2:25][CH2:20][CH2:19]2)=[O:28])[CH:7]=1

Participants

6

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 69.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

4-Amino-6-(2-fluoro-4-nitrophenoxy)pyrimidine (100 mg) was dissolved in tetrahydrofuran (3 ml) under a nitrogen atmosphere, and then triethylamine (0.112 ml) and phenyl chloroformate (0.100 ml) were added dropwise thereto, followed by stirring for 1.5 hrs. To the reaction mixture was added pyrrolidine (0.313 ml), followed by stirring for 30 min. The reaction mixture was partitioned between ethyl acetate and a saturated aqueous solution of ammonium chloride. The organic layer was washed with a saturated aqueous solution of ammonium chloride, water and brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated under a reduced pressure to give a residue, which was then purified by silica gel column chromatography (Fuji Silysia NH, eluent; hexane:ethyl acetate=2:1). The solvent was evaporated under a reduced pressure to give a residue, which was partitioned between ethyl acetate and a 1 N aqueous solution of sodium hydroxide. The organic layer was washed with water and brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated under a reduced pressure to give a residue, which was then dried in vacuum to provide the titled compound (96.6 mg, 69.5%) as a yellow solid.

Workup

  1. stirringby stirring for 30 min
  2. customThe reaction mixture was partitioned between ethyl acetate
  3. washThe organic layer was washed with a saturated aqueous solution of ammonium chloride, water and brine in this order
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was evaporated under a reduced pressure
  6. customto give a residue, which
  7. customwas then purified by silica gel column chromatography (Fuji Silysia NH, eluent; hexane:ethyl acetate=2:1)
  8. customThe solvent was evaporated under a reduced pressure
  9. customto give a residue, which
  10. customwas partitioned between ethyl acetate
  11. washThe organic layer was washed with water and brine in this order
  12. dry with materialdried over anhydrous sodium sulfate
  13. customThe solvent was evaporated under a reduced pressure
  14. customto give a residue, which
  15. customwas then dried in vacuum

Sources & evidence

ORD record
ord-ea7140a470494d4e8a93013637de8313
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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