Cyclopropylamine → N-{4-[6-(Cyclopropylamino)carbonyl-7-methoxy-4-quinolyl]oxyphenyl}-N'-(4-fluorophenyl)urea

HRID 1433599Notes

Reaction equation

HRID 1433599 reaction equation
[F:1][C:2]1[CH:33]=[CH:32][C:5]([NH:6][C:7]([NH:9][C:10]2[CH:31]=[CH:30][C:13]([O:14][C:15]3[C:24]4[C:19](=[CH:20][C:21]([O:28][CH3:29])=[C:22]([C:25](O)=[O:26])[CH:23]=4)[N:18]=[CH:17][CH:16]=3)=[CH:12][CH:11]=2)=[O:8])=[CH:4][CH:3]=1.Cl.C(N=C=N[CH2:40][CH2:41][CH2:42][N:43](CC)CC)C.O.ON1C2C=CC=CC=2N=N1.C1(N)CC1>CN(C)C=O.O.C(OCC)(=O)C.C(N(CC)CC)C>[CH:42]1([NH:43][C:25]([C:22]2[CH:23]=[C:24]3[C:19](=[CH:20][C:21]=2[O:28][CH3:29])[N:18]=[CH:17][CH:16]=[C:15]3[O:14][C:13]2[CH:30]=[CH:31][C:10]([NH:9][C:7]([NH:6][C:5]3[CH:32]=[CH:33][C:2]([F:1])=[CH:3][CH:4]=3)=[O:8])=[CH:11][CH:12]=2)=[O:26])[CH2:40][CH2:41]1

Participants

9

Reactant 4

HCID 69828CyclopropylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 99645121-(3-Diethylaminopropyl)-3-ethylcarbodiimide hydrochlorideHCID 229363504-(4-(((4-Fluoroanilino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxylic acid

Product 1

HCID 58930836N-{4-[6-(Cyclopropylamino)carbonyl-7-methoxy-4-quinolyl]oxyphenyl}-N'-(4-fluorophenyl)ureaYield 44.5%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

After dissolving the N-[4-(6-carboxy-7-methoxy-4-quinolyl)oxyphenyl]-N′-(4-fluorophenyl)urea (60 mg) synthesized in Example 341 in dimethylformamide (1.5 ml), there were added 1-ethyl-3-(3-diethylaminopropyl)-carbodiimide hydrochloride (39 mg), 1-hydroxy-1H-benzotriazole monohydrate (31 mg), triethylamine (30 μl) and cyclopropylamine (0.05 ml) and the mixture was stirred overnight at room temperature. The reaction solution was distributed between ethyl acetate and water, and the organic layer was washed with water and then dried over anhydrous sodium sulfate. After distilling off the solvent, crystals were precipitated with ethyl acetate, filtered out and dried under reduced pressure to obtain the title compound (29 mg) as white crystals.

Workup

  1. washthe organic layer was washed with water
  2. dry with materialdried over anhydrous sodium sulfate
  3. distillationAfter distilling off the solvent, crystals
  4. customwere precipitated with ethyl acetate
  5. filtrationfiltered out
  6. customdried under reduced pressure

Sources & evidence

ORD record
ord-9cf3f2cb7dcb4558b2bab3f82643fb96
Source dataset
uspto-grants-2009_11
Patent number
US07612092B2

Reaction notes

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