Diethyl Ether → HCID 57677416, compound

HRID 492773Notes

Reaction equation

HRID 492773 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]([Cl:37])[CH:17]=1.C(OCC)C>C(#N)C>[Cl: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 23153091HCID 23153091, compound

Product 1

HCID 57677416HCID 57677416, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

2-Phenylacetyl chloride (0.73 ml) was dissolved in acetonitrile (5 ml) under a nitrogen atmosphere, and then potassium thiocyanate (107 mg) was added thereto at 60° C., followed by stirring at the same temperature for 2 hrs. The reaction mixture was cooled down to room temperature, and then a solution of 4-(4-amino-2-chlorophenoxy)-2-[(pyrrolidin-1-yl)carbonylamino]pyridine (122 mg) in acetonitrile (5 ml) was added thereto, followed by stirring at room temperature for 1.5 hr. The reaction mixture was partitioned between ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate. The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate and brine in this order, 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, then ethyl acetate). 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 (66.7 mg, 36%) as pale yellow crystals.

Workup

  1. customat 60° C.
  2. stirringby stirring at room temperature for 1.5 hr
  3. customThe reaction mixture was partitioned between ethyl acetate
  4. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate and brine in this order
  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
  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-2e0edbd0c33949edbd8a29f1d9acf7d8
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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