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

HRID 388033Notes

Reaction equation

HRID 388033 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][C:23]=1[NH:24][C:25]([NH:27][CH3:28])=[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.CN.CO.[CH2:33]([N:35](CC)CC)C.F[P-](F)(F)(F)(F)F.CN([PH+](N(C)C)N(C)C)C>CN(C)C=O.O.C(OCC)(=O)C>[CH3:33][NH:35][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][CH3:28])=[O:26])=[C:2]([Cl:1])[CH:3]=1)=[O:18]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 22494795Tris(dimethylamino)phosphonium hexafluorophosphateHCID 229363674-(3-Chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxylic acidHCID 57454252Monomethylamine methanol

Product 1

HCID 22936898N6-Methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamideYield 82%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

After dissolving 4-(3-chloro-4-(((methylamino) carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxylic acid (100 mg, 0.250 mmol) in dimethylformamide (3 ml), there were added a 40% methylamine-methanol solution (0.100 ml), triethylamine (0.250 ml) and 1H-1,2,3-benzotriazol-1-yloxy)(tri(dimethylamino))phosphonium hexafluorophosphate (221 mg, 0.500 mmol) in that order at room temperature, and the mixture was stirred for 15 hours. 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 magnesium sulfate. The solvent was distilled off, 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 (85.0 mg, 0.204 mmol, 82%) as white crystals.

Workup

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

Sources & evidence

ORD record
ord-aa0299f709c04af8b4b724dfd6adfefa
Source dataset
uspto-grants-2013_02
Patent number
US08372981B2

Reaction notes

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