Triethylamine → 4-(4-Amino-3-chlorophenoxy)-2-[(pyrrolidin-1-yl)carbonylamino]pyridine

HRID 492695Notes

Reaction equation

HRID 492695 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH2:15])=[C:11]([Cl:16])[CH:10]=2)[CH:5]=[CH:4][N:3]=1.[CH2:17]([N:19]([CH2:22][CH3:23])[CH2:20]C)[CH3:18].ClC(OC1C=CC=CC=1)=[O:26].N1CCCC1>O1CCCC1.CCCCCC.C(OCC)(=O)C>[NH2:15][C:12]1[CH:13]=[CH:14][C:9]([O:8][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:1][C:20]([N:19]3[CH2:22][CH2:23][CH2:18][CH2:17]3)=[O:26])[CH:7]=2)=[CH:10][C:11]=1[Cl:16]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 31268PyrrolidineHCID 229367984-(4-Amino-3-chlorophenoxy)pyridin-2-ylamine

Product 1

HCID 231535334-(4-Amino-3-chlorophenoxy)-2-[(pyrrolidin-1-yl)carbonylamino]pyridineYield 35%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

2-Amino-4-(4-amino-3-chlorophenoxy)pyridine (471 mg) as disclosed in WO 02/32872 was dissolved in tetrahydrofuran (10 ml) under a nitrogen atmosphere, and then triethylamine (0.348 ml) and phenyl chloroformate (0.313 ml) were added dropwise thereto while cooling in an ice bath, followed by raising the temperature gradually to room temperature and stirring overnight. To the reaction mixture was added pyrrolidine (2 ml), followed by further stirring for 1 day. The reaction mixture was partitioned between ethyl acetate and water. 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; ethyl acetate). Fractions containing the target compound were concentrated to give a residue, to which hexane-ethyl acetate (5:1) was added to precipitate crystals. The crystals were filtered off, and dried under aeration to provide the titled compound (232 mg, 35%) as white crystals.

Workup

  1. temperaturewhile cooling in an ice bath
  2. stirringby further stirring for 1 day
  3. customThe reaction mixture was partitioned between ethyl acetate and water
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe solvent was evaporated
  7. customto give a residue, which
  8. customwas then purified by silica gel column chromatography (eluent; ethyl acetate)
  9. additionFractions containing the target compound
  10. concentrationwere concentrated
  11. customto give a residue
  12. customto precipitate crystals
  13. filtrationThe crystals were filtered off
  14. customdried under aeration

Sources & evidence

ORD record
ord-225ab78285da4eaea8392d2389fe86f9
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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