Triethylamine → HCID 57677478, compound

HRID 492698Notes

Reaction equation

HRID 492698 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)=[S:26].N1CCCC1>O1CCCC1>[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)=[S:26])[CH:7]=2)=[CH:10][C:11]=1[Cl:16]

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 31268Pyrrolidine2×HCID 70498Phenyl thioxochloroformate2×HCID 229367984-(4-Amino-3-chlorophenoxy)pyridin-2-ylamine

Product 1

HCID 57677478HCID 57677478, compoundYield 19.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-Amino-4-(4-amino-3-chlorophenoxy)pyridine (250 mg) as disclosed in WO 02/32872 was dissolved in tetrahydrofuran (5 ml) under a nitrogen atmosphere, and then triethylamine (0.185 ml) and phenyl chlorothioformate (0.184 ml) were added dropwise thereto while cooling in an ice bath, followed by stirring at room temperature for 2.5 hrs. To the reaction mixture were further added triethylamine (0.074 ml) and phenyl chlorothioformate (0.073 ml), followed by stirring at room temperature for 40 min. To the reaction mixture was added pyrrolidine (0.530 ml), followed by stirring overnight. Pyrrolidine (0.530 ml) was further added thereto, followed by stirring for 1 hr. The reaction mixture was warmed to 40° C. and stirred for 30 min, and warmed to 50° C. and stirred for 2.5 hrs. 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; hexane:ethyl acetate=1:1 to 1:3). Fractions containing the target compound were concentrated to give a residue, which was dried in vacuum to provide the titled compound (73.2 mg, 19.8%) as a colorless solid.

Workup

  1. temperaturewhile cooling in an ice bath
  2. stirringby stirring at room temperature for 40 min
  3. stirringby stirring overnight
  4. stirringby stirring for 1 hr
  5. temperatureThe reaction mixture was warmed to 40° C.
  6. stirringstirred for 30 min
  7. temperaturewarmed to 50° C.
  8. stirringstirred for 2.5 hrs
  9. customThe reaction mixture was partitioned between ethyl acetate and water
  10. washThe organic layer was washed with brine
  11. dry with materialdried over anhydrous sodium sulfate
  12. customThe solvent was evaporated
  13. customto give a residue, which
  14. customwas then purified by silica gel column chromatography (eluent; hexane:ethyl acetate=1:1 to 1:3)
  15. additionFractions containing the target compound
  16. concentrationwere concentrated
  17. customto give a residue, which
  18. customwas dried in vacuum

Sources & evidence

ORD record
ord-1c5da915c89e41a7b9d633eb1324d447
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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