Diisopropylethylamine → N-(1-Fluoropropan-2-yl)-4-[(1E)-3-oxo-3-({2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]-ethyl}amino)prop-1-en-1-yl]-2-(trifluoromethyl)benzamide

HRID 339102Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 339102
[O:1]=[C:2]([NH:18][CH:19]([C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=1)[C:20]([F:23])([F:22])[F:21])/[CH:3]=[CH:4]/[C:5]1[CH:13]=[CH:12][C:8]([C:9](O)=[O:10])=[C:7]([C:14]([F:17])([F:16])[F:15])[CH:6]=1.ClC1C=C(O)C2N=NNC=2C=1.Cl.CN(C)CCCN=C=NCC.C(N(C(C)C)C(C)C)C.Cl.[F:67][CH2:68][CH:69]([NH2:71])[CH3:70]>ClCCl>[F:67][CH2:68][CH:69]([NH:71][C:9](=[O:10])[C:8]1[CH:12]=[CH:13][C:5](/[CH:4]=[CH:3]/[C:2](=[O:1])[NH:18][CH:19]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:31])([F:32])[F:33])[CH:25]=2)[C:20]([F:22])([F:23])[F:21])=[CH:6][C:7]=1[C:14]([F:16])([F:17])[F:15])[CH3:70]

Komponenten

7

Edukt 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 231435941-Fluoropropan-2-amine hydrochlorideHCID 866530664-[(1E)-3-Oxo-3-({2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}amino)prop-1-en-1-yl]-2-(trifluoromethyl)benzoic acidHCID 178516184HCID 178516184, Verbindung

Produkt 1

HCID 58247962N-(1-Fluoropropan-2-yl)-4-[(1E)-3-oxo-3-({2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]-ethyl}amino)prop-1-en-1-yl]-2-(trifluoromethyl)benzamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

49 mg (1 eq, 0.1 mmol) of 4-[(1E)-3-oxo-3-({2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-amino)prop-1-en-1-yl]-2-(trifluoromethyl)benzoic acid from Example 2, Stage 2 were dissolved in 1 ml of dichloromethane. Then 17 mg (1.0 eq, 0.10 mmol) of 6-chlorohydroxybenzotriazole, 23 mg (1.2 eq, 0.12 mmol) of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride and 26 mg (2 eq, 0.20 mmol) of N-ethyldiisopropylamine were added thereto, and the mixture was stirred at RT for 20 min. Subsequently, 11 mg (1.0 eq, 0.10 mmol) of 1-fluoropropan-2-amine hydrochloride were added and the reaction mixture was stirred at room temperature for 12 h. After this time, the reaction mixture was concentrated and the resulting crude product was purified by means of preparative HPLC (phenomenex Gemini C18 5 μm; 110A; AXIA 50×21.2 mm; gradient: 0-2 min 70% water, 30% MeOH, 2.5-6.0 min linear gradient to 5% water, 95% MeOH, 6.0-20.00 min 5% water, 95% MeOH; modifier: 20% HCOOH added at 2 ml/min). This gives 27 mg (37%) of N-(1-fluoropropan-2-yl)-4-[(1E)-3-oxo-3-({2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}amino)-prop-1-en-1-yl]-2-(trifluoromethyl)benzamide as a solid.

Aufarbeitung

  1. stirringthe reaction mixture was stirred at room temperature for 12 h
  2. concentrationAfter this time, the reaction mixture was concentrated
  3. customthe resulting crude product was purified by means of preparative HPLC (phenomenex Gemini C18 5 μm
  4. custom0-2 min 70% water, 30% MeOH, 2.5-6.0 min
  5. customto 5% water, 95% MeOH, 6.0-20.00 min 5% water, 95% MeOH
  6. additionmodifier: 20% HCOOH added at 2 ml/min)

Quellen und Nachweise

ORD-Eintrag
ord-b064c8fdb8a94a559900a627a0ca89b4
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08889878B2

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