Diethyl Ether → 4-{2-Fluoro-4-[3-(2-phenylacetyl)thioureido]phenoxy}-2-[(pyrrolidin-1-yl)carbonylamino]pyridine

HRID 492777Notes

Reaction equation

HRID 492777 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)=[C:18]([F:37])[CH:17]=1.C(OCC)C>C(#N)C>[F:37][C:18]1[CH:17]=[C:16]([NH:15][C:12]([NH:13][C:8](=[O:9])[CH2:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[S:11])[CH:36]=[CH:35][C:19]=1[O:20][C:21]1[CH:26]=[CH:25][N:24]=[C:23]([NH:27][C:28]([N:30]2[CH2:31][CH2:32][CH2:33][CH2:34]2)=[O:29])[CH:22]=1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 7679Phenylacetyl chlorideHCID 516872Potassium thiocyanateHCID 231530584-(4-Amino-2-fluorophenoxy)-2-[(pyrrolidin-1-yl)carbonylamino]pyridine

Product 1

HCID 576775874-{2-Fluoro-4-[3-(2-phenylacetyl)thioureido]phenoxy}-2-[(pyrrolidin-1-yl)carbonylamino]pyridineYield 34%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

2-Phenylacetyl chloride (100 mg) was dissolved in acetonitrile (2 ml) under a nitrogen atmosphere, and then potassium thiocyanate (126 mg) was added thereto at 50° C., followed by stirring at the same temperature for 1.5 hrs. A solution of 4-(4-amino-2-fluorophenoxy)-2-[(pyrrolidin-1-yl)carbonylamino]pyridine (41 mg) in acetonitrile (4 ml) was added thereto, followed by stirring at room temperature for 2.5 hr. The reaction mixture was cooled down to room temperature, and then partitioned between ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate. The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under a reduced pressure to give a residue, which was then purified by silica gel column chromatography (eluent; hexane:ethyl acetate=1:4). Fractions containing the target compound were concentrated to give a residue, to which a small amount of diethyl ether was added to precipitate crystals. A suspension containing the crystals was diluted with a small amount of hexane. The crystals were filtered off and dried under aeration to provide the titled compound (21.4 mg, 34%) as pale yellow crystals.

Workup

  1. customat 50° C.
  2. stirringby stirring at room temperature for 2.5 hr
  3. custompartitioned between ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe solvent was evaporated under a reduced pressure
  7. customto give a residue, which
  8. customwas then purified by silica gel column chromatography (eluent; hexane:ethyl acetate=1:4)
  9. additionFractions containing the target compound
  10. concentrationwere concentrated
  11. customto give a residue
  12. customto precipitate crystals
  13. additionA suspension containing the crystals
  14. additionwas diluted with a small amount of hexane
  15. filtrationThe crystals were filtered off
  16. customdried under aeration

Sources & evidence

ORD record
ord-9bb397c451474c3f9717ce249a7a084f
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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