Benzeneacetamide → 4-{2-Fluoro-4-[3-(2-phenylacetyl)ureido]phenoxy}-2-[(pyrrolidin-1-yl)carbonylamino]pyridine

HRID 492802Notes

Reaction equation

HRID 492802 reaction equation
[C:1]1([CH2:7][C:8]([NH2:10])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(Cl)(=O)[C:12](Cl)=[O:13].[NH2:17][C:18]1[CH:38]=[CH:37][C:21]([O:22][C:23]2[CH:28]=[CH:27][N:26]=[C:25]([NH:29][C:30]([N:32]3[CH2:36][CH2:35][CH2:34][CH2:33]3)=[O:31])[CH:24]=2)=[C:20]([F:39])[CH:19]=1.C(OCC)(=O)C>ClCCCl.CN(C)C=O.CCCCCC>[F:39][C:20]1[CH:19]=[C:18]([NH:17][C:12]([NH:10][C:8](=[O:9])[CH2:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[O:13])[CH:38]=[CH:37][C:21]=1[O:22][C:23]1[CH:28]=[CH:27][N:26]=[C:25]([NH:29][C:30]([N:32]2[CH2:33][CH2:34][CH2:35][CH2:36]2)=[O:31])[CH:24]=1

Participants

8

Reactant 4

HCID 7680BenzeneacetamideHCID 8857Ethyl AcetateHCID 65578Oxalyl chlorideHCID 231530584-(4-Amino-2-fluorophenoxy)-2-[(pyrrolidin-1-yl)carbonylamino]pyridine

Product 1

HCID 231529864-{2-Fluoro-4-[3-(2-phenylacetyl)ureido]phenoxy}-2-[(pyrrolidin-1-yl)carbonylamino]pyridineYield 75%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolventHCID 8058HexaneSolvent

Conditions

Temperature
120 °C

Procedure

2-Phenylacetamide (128 mg) was dissolved in 1,2-dichloroethane (10 ml) under a nitrogen atmosphere, and then oxalyl chloride (0.103 ml) was added thereto, followed by stirring at 120° C. overnight. The reaction mixture was concentrated under a reduced pressure to give a residue, which was then dissolved in N,N-dimethylformamide (3.2 ml) under a nitrogen atmosphere. 4-(4-amino-2-fluorophenoxy)-2-[(pyrrolidin-1-yl)carbonylamino]pyridine (100 mg) was then added thereto, followed by stirring for 30 min. The reaction mixture was partitioned between ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate. The organic layer was washed with water and brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was purified by silica gel column chromatography (FUJI Silysia NH, eluent; hexane:ethyl acetate=1:3). Fractions containing the target compound were concentrated to give a residue, to which ethyl acetate (2 ml)-hexane (10 ml) was added to precipitate crystals. The crystals were filtered off and dried under aeration to provide the titled compound (113 mg, 75%) as white crystals.

Workup

  1. concentrationThe reaction mixture was concentrated under a reduced pressure
  2. customto give a residue, which
  3. stirringby stirring for 30 min
  4. customThe reaction mixture was partitioned between ethyl acetate
  5. washThe organic layer was washed with water and brine in this order
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was evaporated
  8. customto give a residue, which
  9. customwas purified by silica gel column chromatography (FUJI Silysia NH, eluent; hexane:ethyl acetate=1:3)
  10. additionFractions containing the target compound
  11. concentrationwere concentrated
  12. customto give a residue
  13. customto precipitate crystals
  14. filtrationThe crystals were filtered off
  15. customdried under aeration

Sources & evidence

ORD record
ord-899c1e95865c42bb86f2773c876ed9c8
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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