Triethylamine → N-[4-(4-Amino-3-fluorophenoxy)-2-pyridinyl]-1-pyrrolidinecarboxamide

HRID 492736Notes

Reaction equation

HRID 492736 reaction equation
[NH2:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH2:13])[CH:8]=2)=[CH:4][C:3]=1[F:16].[CH2:17]([N:19]([CH2:22][CH3:23])[CH2:20]C)[CH3:18].ClC(OC1C=CC=CC=1)=[O:26].N1CCCC1>O1CCCC1.CN(C)C=O>[NH2:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:20]([N:19]3[CH2:22][CH2:23][CH2:18][CH2:17]3)=[O:26])[CH:8]=2)=[CH:4][C:3]=1[F:16]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 31268PyrrolidineHCID 71470884-(4-Amino-3-fluorophenoxy)pyridin-2-amine

Product 1

HCID 57677638N-[4-(4-Amino-3-fluorophenoxy)-2-pyridinyl]-1-pyrrolidinecarboxamideYield 13%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-(4-amino-3-fluorophenoxy)pyridin-2-ylamine (500 mg) in tetrahydrofuran (10 ml) was added triethylamine (0.223 ml), and then phenyl chloroformate (0.200 ml) was added thereto while stirring in an ice bath, followed by stirring under a nitrogen atmosphere for 2 hr. The reaction mixture was concentrated under a reduced pressure to give a residue, to which N,N-dimethylformamide (10 ml) and pyrrolidine (0.667 ml) were then added, followed by stirring at room temperature for 21 hrs. The reaction mixture was partitioned between ethyl acetate (100 ml) and water (100 ml). The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (eluent; hexane:ethyl acetate=1:2, ethyl acetate, then ethyl acetate:methanol=10:1). Fractions containing the target compound were concentrated to provide the titled compound (94 mg, 13%) as a purple oil.

Workup

  1. stirringby stirring under a nitrogen atmosphere for 2 hr
  2. concentrationThe reaction mixture was concentrated under a reduced pressure
  3. customto give a residue
  4. stirringby stirring at room temperature for 21 hrs
  5. customThe reaction mixture was partitioned between ethyl acetate (100 ml) and water (100 ml)
  6. washThe organic layer was washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. customThe solvent was evaporated
  9. customto give a residue, which
  10. customwas then purified by silica gel column chromatography (eluent
  11. additionFractions containing the target compound
  12. concentrationwere concentrated

Sources & evidence

ORD record
ord-97043eeddef842a48711db28ee259bb1
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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