Triethylamine → N6-(2-Ethoxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide

HRID 387911Notes

Reaction equation

HRID 387911 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.[CH2:31]([O:33][CH2:34][CH2:35][NH2:36])[CH3:32].C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C)C=O.O.C(OCC)(=O)C>[CH2:31]([O:33][CH2:34][CH2:35][NH:36][C:16]([C:13]1[CH:14]=[C:15]2[C:10](=[CH:11][C:12]=1[O:19][CH3:20])[N:9]=[CH:8][CH:7]=[C:6]2[O:5][C:4]1[CH:21]=[CH:22][C:23]([NH:24][C:25]([NH:27][CH:28]2[CH2:29][CH2:30]2)=[O:26])=[C:2]([Cl:1])[CH:3]=1)=[O:18])[CH3:32]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 66970EthoxyethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 22936749Lenvatinib Impurity F

Product 1

HCID 22936710N6-(2-Ethoxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamideYield 88%

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) under a nitrogen atmosphere, 2-ethoxyethylamine (0.042 ml, 0.40 mmol), triethylamine (0.2 ml) and ((1H-1,2,3-benzotriazol-1-yloxy)(tri(dimethylamino)) phosphonium hexafluorophosphate) (133 mg, 0.20 mmol) were added in that order at room temperature, and the mixture was stirred overnight. The reaction solution was distributed between ethyl acetate and water, and the organic layer was washed with water and saturated saline and dried over anhydrous sodium sulfate. The solvent was distilled off and suspended in ethyl acetate, the suspension was diluted with hexane, and the crystals were filtered out and blow-dried to obtain the title compound (87.7 mg, 0.176 mmol, 87.9%) as white crystals.

Workup

  1. washthe organic layer was washed with water and saturated saline
  2. dry with materialdried over anhydrous sodium sulfate
  3. distillationThe solvent was distilled off
  4. additionthe suspension was diluted with hexane
  5. filtrationthe crystals were filtered out and
  6. customblow-dried

Sources & evidence

ORD record
ord-5574a9ffd88646bbbd07cc846e017bfa
Source dataset
uspto-grants-2013_02
Patent number
US08372981B2

Reaction notes

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