Dimethylformamide → HCID 16118248, compound

HRID 2265629Notes

Reaction equation

HRID 2265629 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:31]=[CH:32][C:33]=1[NH:34][C:35]([C:37]1([C:40](=[O:49])[NH:41][C:42]2[CH:47]=[CH:46][C:45]([F:48])=[CH:44][CH:43]=2)[CH2:39][CH2:38]1)=[O:36])[O:5][C:6]1[CH:11]=[CH:10][N:9]=[C:8]([N:12](C(OC2C=CC=CC=2)=O)C(=O)OC2C=CC=CC=2)[CH:7]=1.[CH3:50][N:51]1[CH2:56][CH2:55]C(NC)[CH2:53][CH2:52]1.[CH3:59][N:60]([CH3:63])[CH:61]=[O:62]>>[F:1][C:2]1[CH:3]=[C:4]([O:5][C:6]2[CH:11]=[CH:10][N:9]=[C:8]([NH:12][C:61]([N:60]([CH3:63])[CH:59]3[CH2:55][CH2:56][N:51]([CH3:50])[CH2:52][CH2:53]3)=[O:62])[CH:7]=2)[CH:31]=[CH:32][C:33]=1[NH:34][C:35]([C:37]1([C:40]([NH:41][C:42]2[CH:43]=[CH:44][C:45]([F:48])=[CH:46][CH:47]=2)=[O:49])[CH2:38][CH2:39]1)=[O:36]

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 5663231-Methyl-4-(methylamino)piperidineHCID 59597026[4-(3-fluoro-4-{[1-(4-fluorophenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridin-2-yl]-N-(phenoxycarbonyl)carbamic acid phenyl ester

Product 1

HCID 16118248HCID 16118248, compoundYield 60.1%

Procedure

To a solution of phenyl N-[4-(3-fluoro-4-{[1-(4-fluorophenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridin-2-yl]-N-phenoxycarbonylcarbamate (50.0 mg) in N,N-dimethylformamide (1.0 ml) was added 1-methyl-4-(methylamino)piperidine (0.0436 ml), followed by stirring at room temperature for 16 hr. The reaction mixture was partitioned between ethyl acetate and a 1N aqueous solution of sodium hydroxide. The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was removed, and the residue was purified by silica gel column chromatography (Fuji Silysia NH, heptane:ethyl acetate=1:2, ethyl acetate, then ethyl acetate:methanol=50:1). Fractions containing the target compound were concentrated. To the residue was added diethyl ether:hexane=1:3, and the precipitate was collected by filtration. This was washed with diethyl ether:hexane=1:3 and dried under aeration to provide the titled compound as white powder (26.1 mg, 60.1%).

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was removed
  5. customthe residue was purified by silica gel column chromatography (Fuji Silysia NH, heptane
  6. additionFractions containing the target compound
  7. concentrationwere concentrated
  8. additionTo the residue was added diethyl ether
  9. filtrationhexane=1:3, and the precipitate was collected by filtration
  10. washThis was washed with diethyl ether
  11. dry with materialhexane=1:3 and dried under aeration

Sources & evidence

ORD record
ord-61c205cc56de4ac1b836257e0fe3a054
Source dataset
uspto-grants-2010_12
Patent number
US07855290B2

Reaction notes

Loading…