Benzeneacetamide → Pyrrolidine-1-carboxylic acid {6-[2-fluoro-4-(3-phenylacetylureido)phenoxy]pyrimidin-4-yl}amide

HRID 492805Notes

Reaction equation

HRID 492805 reaction equation
C1(CC(N)=O)C=CC=CC=1.C(Cl)(=O)C(Cl)=O.[C:17]1([CH2:23][C:24]([N:26]=[C:27]=[O:28])=[O:25])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[NH2:29][C:30]1[CH:50]=[CH:49][C:33]([O:34][C:35]2[N:40]=[CH:39][N:38]=[C:37]([NH:41][C:42]([N:44]3[CH2:48][CH2:47][CH2:46][CH2:45]3)=[O:43])[CH:36]=2)=[C:32]([F:51])[CH:31]=1>ClC(Cl)C.CCCCCC.CN(C)C=O.C(OCC)(=O)C>[F:51][C:32]1[CH:31]=[C:30]([NH:29][C:27]([NH:26][C:24](=[O:25])[CH2:23][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:28])[CH:50]=[CH:49][C:33]=1[O:34][C:35]1[N:40]=[CH:39][N:38]=[C:37]([NH:41][C:42]([N:44]2[CH2:48][CH2:47][CH2:46][CH2:45]2)=[O:43])[CH:36]=1

Participants

9

Reactant 4

HCID 7680BenzeneacetamideHCID 65578Oxalyl chlorideHCID 12259960Phenylacetyl isocyanate2×HCID 231534594-(4-Amino-2-fluorophenoxy)-6-[(pyrrolidin-1-yl)carbonylamino]pyrimidine

Product 1

HCID 57677321Pyrrolidine-1-carboxylic acid {6-[2-fluoro-4-(3-phenylacetylureido)phenoxy]pyrimidin-4-yl}amideYield 78.1%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolventHCID 63651,1-DichloroethaneSolventHCID 8058HexaneSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

To a suspension of 2-phenylacetamide (905 mg, 6.7 mmol) in dichloroethane (90 ml) was added oxalyl chloride (1.75 ml, 20.1 mmol) under a nitrogen atmosphere, followed by stirring at 110° C. for 12 hrs. The reaction mixture was cooled down to room temperature, and concentrated under a reduced pressure to give a residue, to which hexane (13.4 ml) was added to prepare a solution of phenylacetyl isocyanate in hexane. To a solution of pyrrolidine-1-carboxylic acid [6-(4-amino-2-fluorophenoxy)pyrimidin-4-yl]amide (40 mg) in N,N-dimethylformamide (1.0 ml) was added the above solution of phenylacetyl isocyanate in hexane (supernatant, 0.948 ml) under a nitrogen atmosphere, followed by stirring at room temperature for 1 hr. The reaction mixture was partitioned between ethyl acetate (50 ml) and a saturated aqueous solution of sodium hydrogencarbonate (20 ml). The organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, to which ethyl acetate (1.0 ml) was added to suspend. The solid was filtered off, washed with diethyl ether, and dried under aeration to provide the titled compound (47.1 mg, 78.1%) as pale yellow powder.

Workup

  1. temperatureThe reaction mixture was cooled down to room temperature
  2. concentrationconcentrated under a reduced pressure
  3. customto give a residue
  4. stirringby stirring at room temperature for 1 hr
  5. customThe reaction mixture was partitioned between ethyl acetate (50 ml)
  6. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  7. customThe solvent was evaporated
  8. customto give a residue
  9. filtrationThe solid was filtered off
  10. washwashed with diethyl ether
  11. customdried under aeration

Sources & evidence

ORD record
ord-e9f6e2e2b4c940109d6f7fe795de47c0
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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