Morpholine → HCID 59596995, compound

HRID 2066296Notes

Reaction equation

HRID 2066296 reaction equation
C1([O:7][C:8](=O)[N:9]([C:19]2[CH:24]=[C:23]([O:25][C:26]3[CH:31]=[CH:30][C:29]([NH:32][C:33]([C:35]4([C:38](=[O:47])[NH:39][C:40]5[CH:45]=[CH:44][C:43]([F:46])=[CH:42][CH:41]=5)[CH2:37][CH2:36]4)=[O:34])=[CH:28][C:27]=3[F:48])[CH:22]=[CH:21][N:20]=2)C(OC2C=CC=CC=2)=O)C=CC=CC=1.[NH:50]1[CH2:55][CH2:54][O:53][CH2:52][CH2:51]1>CN(C)C=O>[F:48][C:27]1[CH:28]=[C:29]([NH:32][C:33]([C:35]2([C:38]([NH:39][C:40]3[CH:41]=[CH:42][C:43]([F:46])=[CH:44][CH:45]=3)=[O:47])[CH2:37][CH2:36]2)=[O:34])[CH:30]=[CH:31][C:26]=1[O:25][C:23]1[CH:22]=[CH:21][N:20]=[C:19]([NH:9][C:8]([N:50]2[CH2:55][CH2:54][O:53][CH2:52][CH2:51]2)=[O:7])[CH:24]=1

Participants

4

Reactant 2

HCID 8083MorpholineHCID 59597000[4-(2-Fluoro-4-{[1-(4-fluorophenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridin-2-yl]-N-(phenoxycarbonyl)carbamic acid phenyl ester

Product 1

HCID 59596995HCID 59596995, compoundYield 81%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of [4-(2-fluoro-4-{[1-(4-fluorophenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridin-2-yl]-N-(phenoxycarbonyl)carbamic acid phenyl ester (80 mg) in N,N-dimethylformamide (1.0 ml) was added morpholine (0.055 ml) at room temperature, followed by stirring overnight. The reaction mixture was partitioned between ethyl acetate and water. 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 concentrated under reduced pressure. The resultant residue was purified by silica gel column chromatography (eluent; ethyl acetate). Fractions containing the target compound were concentrated under reduced pressure. To the resultant residue was added diethyl ether:heptane=1:2 to precipitate a solid. The solvent was concentrated under reduced pressure to provide the titled compound as white powder (52.3 mg, 81%).

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and water
  2. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate and brine in this order
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationThe solvent was concentrated under reduced pressure
  5. customThe resultant residue was purified by silica gel column chromatography (eluent; ethyl acetate)
  6. additionFractions containing the target compound
  7. concentrationwere concentrated under reduced pressure
  8. additionTo the resultant residue was added diethyl ether
  9. customheptane=1:2 to precipitate a solid
  10. concentrationThe solvent was concentrated under reduced pressure

Sources & evidence

ORD record
ord-9c1a39f2b86048e985e71fb88ae60d2c
Source dataset
uspto-grants-2012_10
Patent number
US08288538B2

Reaction notes

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