Triethylamine → N6-Cyclopropyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide

HRID 1010286Notes

Reaction equation

HRID 1010286 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][C:23]=1[NH:24][C:25]([NH:27][CH:28]1[CH2:30][CH2:29]1)=[O:26])[O:5][C:6]1[C:15]2[C:10](=[CH:11][C:12]([O:19][CH3:20])=[C:13]([C:16]([OH:18])=O)[CH:14]=2)[N:9]=[CH:8][CH:7]=1.Cl.C(N=C=N[CH2:37][CH2:38][CH2:39][N:40](C)C)C.O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.C1(N)CC1>CN(C)C=O.O.C(OCC)(=O)C>[CH:39]1([NH:40][C:16]([C:13]2[CH:14]=[C:15]3[C:10](=[CH:11][C:12]=2[O:19][CH3:20])[N:9]=[CH:8][CH:7]=[C:6]3[O:5][C:4]2[CH:21]=[CH:22][C:23]([NH:24][C:25]([NH:27][CH:28]3[CH2:29][CH2:30]3)=[O:26])=[C:2]([Cl:1])[CH:3]=2)=[O:18])[CH2:37][CH2:38]1

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 69828CyclopropylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 22936749Lenvatinib Impurity F

Product 1

HCID 11561795N6-Cyclopropyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamideYield 43%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

After dissolving 4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxylic acid (86 mg, 0.20 mmol) in dimethylformamide (2 ml), there were added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (77 mg, 0.40 mmol), 1-hydroxy-1H-benzotriazole monohydrate (61 mg, 0.40 mmol), triethylamine (0.112 ml, 0.80 mmol) and cyclopropylamine (0.055 ml) while stirring on ice, 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 saturated brine and then dried over anhydrous sodium sulfate. After distilling off the solvent, the residue was suspended in ethyl acetate and diluted with hexane, and the crystals were filtered out and blow-dried to obtain the title compound (40.0 mg, 0.086 mmol, 42.6%) as white crystals.

Workup

  1. stirringthe mixture was stirred overnight at room temperature
  2. washthe organic layer was washed with water and saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. distillationAfter distilling off the solvent
  5. additiondiluted with hexane
  6. filtrationthe crystals were filtered out and
  7. customblow-dried

Sources & evidence

ORD record
ord-7c7a3a8b3911413caa44b559393b0315
Source dataset
uspto-grants-2011_07
Patent number
US07973160B2

Reaction notes

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