Phenylacetyl chloride → Pyrrolidine-1-carboxylic acid {4-[3-fluoro-4-(3-phenylacetylthioureido)phenoxy]pyridin-2-yl}amide

HRID 492782Notes

Reaction equation

HRID 492782 reaction equation
[C:1]1([CH2:7][C:8](Cl)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[S-:11][C:12]#[N:13].[K+].[NH2:15][C:16]1[CH:36]=[CH:35][C:19]([O:20][C:21]2[CH:26]=[CH:25][N:24]=[C:23]([NH:27][C:28]([N:30]3[CH2:34][CH2:33][CH2:32][CH2:31]3)=[O:29])[CH:22]=2)=[CH:18][C:17]=1[F:37]>C(#N)C.C(OCC)C>[F:37][C:17]1[CH:18]=[C:19]([CH:35]=[CH:36][C:16]=1[NH:15][C:12]([NH:13][C:8](=[O:9])[CH2:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)=[S:11])[O:20][C:21]1[CH:26]=[CH:25][N:24]=[C:23]([NH:27][C:28]([N:30]2[CH2:34][CH2:33][CH2:32][CH2:31]2)=[O:29])[CH:22]=1

Participants

6

Reactant 3

HCID 7679Phenylacetyl chlorideHCID 516872Potassium thiocyanateHCID 57677638N-[4-(4-Amino-3-fluorophenoxy)-2-pyridinyl]-1-pyrrolidinecarboxamide

Product 1

HCID 57677648Pyrrolidine-1-carboxylic acid {4-[3-fluoro-4-(3-phenylacetylthioureido)phenoxy]pyridin-2-yl}amideYield 13%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolvent2×

Conditions

Temperature
60 °C

Procedure

To a solution of 2-phenylacetyl chloride (0.054 ml, 0.43 mmol) in acetonitrile (4.3 ml) was added potassium thiocyanate (83 mg) at room temperature, followed by stirring under a nitrogen atmosphere at 60° C. for 1.5 hrs. The reaction mixture was cooled in an ice bath, and then a solution of pyrrolidine-1-carboxylic acid [4-(4-amino-3-fluorophenoxy)pyridin-2-yl]amide (90 mg) in acetonitrile (4.0 ml) was added thereto, followed by warming the reaction mixture to room temperature and stirring for 3 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 1:2, then ethyl acetate). Fractions containing the target compound were concentrated to give a solid, which was suspended in diethyl ether. The solid was filtered off, washed with diethyl ether, and dried under aeration to provide the titled compound (18 mg, 13%) as colorless powder.

Workup

  1. temperatureThe reaction mixture was cooled in an ice bath
  2. temperatureby warming the reaction mixture to room temperature
  3. stirringstirring for 3 hrs
  4. customThe reaction mixture was partitioned between ethyl acetate and water
  5. washThe organic layer was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was evaporated
  8. customto give a residue, which
  9. customwas then purified by silica gel column chromatography (eluent
  10. additionFractions containing the target compound
  11. concentrationwere concentrated
  12. customto give a solid, which
  13. filtrationThe solid was filtered off
  14. washwashed with diethyl ether
  15. customdried under aeration

Sources & evidence

ORD record
ord-e4f3f547c5244df7a3bb12b8a4625f9f
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

Loading…