Trifluoroacetic acid → HCID 178509950, Verbindung

HRID 1875064Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1875064
[NH2:1][CH2:2][C:3]1[C:4]([F:20])=[C:5]([O:10][C:11]2[CH:12]=[C:13]([CH:16]=[C:17]([Cl:19])[CH:18]=2)[C:14]#[N:15])[C:6]([Cl:9])=[CH:7][CH:8]=1.CC(OC([N:28](C(OC(C)(C)C)=O)[C:29]1[NH:30][C:31]([C:35](O)=[O:36])=[C:32]([Cl:34])[N:33]=1)=O)(C)C.ClC1N=C(NC(OC(C)(C)C)=O)NC=1C(O)=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[C:95]([OH:101])([C:97]([F:100])([F:99])[F:98])=[O:96]>CN(C=O)C>[F:98][C:97]([F:100])([F:99])[C:95]([OH:101])=[O:96].[NH2:28][C:29]1[NH:30][C:31]([C:35]([NH:1][CH2:2][C:3]2[CH:8]=[CH:7][C:6]([Cl:9])=[C:5]([O:10][C:11]3[CH:12]=[C:13]([C:14]#[N:15])[CH:16]=[C:17]([Cl:19])[CH:18]=3)[C:4]=2[F:20])=[O:36])=[C:32]([Cl:34])[N:33]=1

Komponenten

8

Edukt 6

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 594513923-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrileHCID 178452983HCID 178452983, VerbindungHCID 178454348HCID 178454348, Verbindung

Produkt 1

HCID 178509950HCID 178509950, VerbindungAusbeute 6,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A mixture of 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.041 g, 0.131 mmol), a 50:50 mixture of 2-(bis{[(1,1-dimethylethyl)oxy]carbonyl}amino)-4-chloro-1H-imidazole-5-carboxylic acid and 4-chloro-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-1H-imidazole-5-carboxylic acid (0.047 g, 0.131 mmol), HATU (0.060 g, 0.157 mmol) and DIPEA (0.027 ml, 0.157 mmol) in DMF (1.5 mL) was stirred at RT overnight. The reaction mixture was extracted between EtOAc and water. The organic layer was washed with water and dried over sodium sulfate. The solvent was evaporated and the crude product was dissolved in dichloromethane (2 mL) and TFA (0.5 ml, 6.49 mmol) was added. The mixture was stirred at RT overnight. The solvent was evaporated and the residue was purified by reverse phase HPLC (acetonitrile:water with 0.1% TFA) to give the title compound (0.007 g, 6.2%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.56 (dd, 1H), 7.41-7.52 (m, 3H), 6.66 (s, 1H), 3.73 (s, 2H), 1.88 (br. s., 2H). ES MS: m/z 454 (M+1)

Aufarbeitung

  1. extractionThe reaction mixture was extracted between EtOAc and water
  2. washThe organic layer was washed with water
  3. dry with materialdried over sodium sulfate
  4. customThe solvent was evaporated
  5. dissolutionthe crude product was dissolved in dichloromethane (2 mL)
  6. stirringThe mixture was stirred at RT overnight
  7. customThe solvent was evaporated
  8. customthe residue was purified by reverse phase HPLC (acetonitrile:water with 0.1% TFA)

Quellen und Nachweise

ORD-Eintrag
ord-38f58573ccd4423cb6231dceca774332
Quelldatensatz
uspto-grants-2012_11
Patentnummer
US08304419B2

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