Ethanol → Pyrrolidine-1-carboxylic acid (4-{2-methyl-4-[3-(4-fluorophenyl)acetylthioureido]phenoxy}pyridin-2-yl)amide

HRID 492788Notes

Reaction equation

HRID 492788 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9](Cl)=[O:10])=[CH:4][CH:3]=1.[S-:12][C:13]#[N:14].[K+].[NH2:16][C:17]1[CH:37]=[CH:36][C:20]([O:21][C:22]2[CH:27]=[CH:26][N:25]=[C:24]([NH:28][C:29]([N:31]3[CH2:35][CH2:34][CH2:33][CH2:32]3)=[O:30])[CH:23]=2)=[C:19]([CH3:38])[CH:18]=1.C(O)C>C(#N)C.C(OCC)C>[CH3:38][C:19]1[CH:18]=[C:17]([NH:16][C:13]([NH:14][C:9](=[O:10])[CH2:8][C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)=[S:12])[CH:37]=[CH:36][C:20]=1[O:21][C:22]1[CH:27]=[CH:26][N:25]=[C:24]([NH:28][C:29]([N:31]2[CH2:35][CH2:34][CH2:33][CH2:32]2)=[O:30])[CH:23]=1

Participants

7

Reactant 4

HCID 702EthanolHCID 516872Potassium thiocyanateHCID 37449884-Fluorophenylacetyl chlorideHCID 57677322Pyrrolidine-1-carboxylic acid [4-(4-amino-2-methylphenoxy)pyridin-2-yl]amide

Product 1

HCID 57677672Pyrrolidine-1-carboxylic acid (4-{2-methyl-4-[3-(4-fluorophenyl)acetylthioureido]phenoxy}pyridin-2-yl)amideYield 11.5%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 2-(4-fluorophenyl)acetyl chloride (66.3 mg) in acetonitrile (30 ml) was added potassium thiocyanate (37.3 mg), followed by stirring under a nitrogen atmosphere at 50° C. for 1 hr. The reaction mixture was cooled down to room temperature, and then pyrrolidine-1-carboxylic acid [4-(4-amino-2-methylphenoxy)pyridin-2-yl]amide (80 mg) was added thereto, followed by stirring under a nitrogen atmosphere for 2 hrs. The reaction mixture was partitioned between ethyl acetate (100 ml) and water (60 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=1:3, then ethyl acetate). Fractions containing the target compound were concentrated to give a residue, to which diethyl ether was then added and concentrated under a reduced pressure again to give a solid. The resultant solid was then suspended in diethyl ether (4 ml)-ethanol (0.4 ml), filtered off, washed with diethyl ether, and dried under aeration to provide the titled compound (15 mg, 11.5%) as colorless powder.

Workup

  1. temperatureThe reaction mixture was cooled down to room temperature
  2. stirringby stirring under a nitrogen atmosphere for 2 hrs
  3. customThe reaction mixture was partitioned between ethyl acetate (100 ml) and water (60 ml)
  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
  9. additionFractions containing the target compound
  10. concentrationwere concentrated
  11. customto give a residue
  12. concentrationconcentrated under a reduced pressure again
  13. customto give a solid
  14. filtrationfiltered off
  15. washwashed with diethyl ether
  16. customdried under aeration

Sources & evidence

ORD record
ord-15ccc32a9c2148ed8c08e81a0f37011a
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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