Triethylamine → tert-Butyl 4-((((4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolyl)carbonyl)amino)methyl)-1-piperidinecarboxylate

HRID 1010398Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1010398
[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.[NH2:31][CH2:32][CH:33]1[CH2:38][CH2:37][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:35][CH2:34]1.C(N(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>[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[CH2:29][CH2:30]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]([NH:31][CH2:32][CH:33]3[CH2:38][CH2:37][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:35][CH2:34]3)=[O:18])[CH:14]=2)[N:9]=[CH:8][CH:7]=1

Komponenten

8

Edukt 4

HCID 8471TriethylamineHCID 7368171-Boc-4-(aminomethyl)piperidineHCID 22494795Tris(dimethylamino)phosphonium hexafluorophosphateHCID 22936749Lenvatinib Impurity F

Produkt 1

HCID 22936930tert-Butyl 4-((((4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolyl)carbonyl)amino)methyl)-1-piperidinecarboxylate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

4-(3-Chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxylic acid) (171 mg, 0.40 mmol) was dissolved in dimethylformamide (4 ml) under a nitrogen atmosphere, and then tert-butyl 4-aminomethyl-1-piperidinecarboxylate (171 mg, 0.80 mmol), triethylamine (0.2 ml) and 1H-1,2,3-benzotriazol-1-yloxy)(tri(dimethylamino))phosphonium hexafluorophosphate (265 mg, 0.60 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 brine and dried over anhydrous sodium 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 (249 mg, quantitative) as white crystals.

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-c285258c19ac4a38a72836b0fc02d3c6
Quelldatensatz
uspto-grants-2011_07
Patentnummer
US07973160B2

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