Dimethylformamide → HCID 16118805, compound

HRID 2066246Notes

Reaction equation

HRID 2066246 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:48])[NH:41][C:42]2[CH:47]=[CH:46][CH:45]=[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.[CH2:49]([N:51]1[CH2:56][CH2:55]C(NC)[CH2:53][CH2:52]1)[CH3:50].[CH3:59][N:60]([CH3:63])[CH:61]=[O:62]>>[CH2:49]([N:51]1[CH2:56][CH2:55][CH:59]([N:60]([CH3:63])[C:61]([NH:12][C:8]2[CH:7]=[C:6]([O:5][C:4]3[CH:31]=[CH:32][C:33]([NH:34][C:35]([C:37]4([C:40]([NH:41][C:42]5[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=5)=[O:48])[CH2:39][CH2:38]4)=[O:36])=[C:2]([F:1])[CH:3]=3)[CH:11]=[CH:10][N:9]=2)=[O:62])[CH2:53][CH2:52]1)[CH3:50]

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 167704711-Ethyl-N-methyl-4-piperidinamineHCID 59596979phenyl N-[4-(3-fluoro-4-{[1-(phenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridin-2-yl]-N-phenoxycarbonylcarbamate

Product 1

HCID 16118805HCID 16118805, compoundYield 58%

Procedure

To phenyl N-[4-(3-fluoro-4-{[1-(phenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridin-2-yl]-N-phenoxycarbonylcarbamate (50.0 mg) was added a solution of N-(1-ethylpiperidin-4-yl)-N-methylamine (66 mg) in N,N-dimethylformamide (1.0 ml), followed by stirring at room temperature for 9 hr. The reaction mixture was partitioned between ethyl acetate and 1N 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, ethyl acetate, then ethyl acetate:methanol=98:2). Fractions containing the target compound were concentrated. A solid was precipitated by addition of diethyl ether:hexane=1:2 to the residue. The solid was collected by filtration and dried under aeration to provide the titled compound as white powder (25.8 mg, 58%).

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and 1N sodium hydroxide
  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, ethyl acetate
  6. additionFractions containing the target compound
  7. concentrationwere concentrated
  8. customA solid was precipitated by addition of diethyl ether
  9. filtrationThe solid was collected by filtration
  10. customdried under aeration

Sources & evidence

ORD record
ord-8e72afba8e9c478e8e6a90840ff3e200
Source dataset
uspto-grants-2012_10
Patent number
US08288538B2

Reaction notes

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