Potassium Hydroxide → (R)-Methyl 5-((5-((4-methylpiperazin-1-yl)methyl)-2-nitrophenyl)amino)-3-(1-(2-(trifluoromethyl)phenyl)ethoxy)thiophene-2-carboxylate

HRID 883574Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 883574
F[C:2]1[CH:3]=[C:4]([CH2:11][N:12]2[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]2)[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9].[NH2:19][C:20]1[S:24][C:23]([C:25]([O:27][CH3:28])=[O:26])=[C:22]([O:29][C@@H:30]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=2[C:38]([F:41])([F:40])[F:39])[CH3:31])[CH:21]=1.[OH-].[K+]>C(#N)C>[CH3:18][N:15]1[CH2:16][CH2:17][N:12]([CH2:11][C:4]2[CH:5]=[CH:6][C:7]([N+:8]([O-:10])=[O:9])=[C:2]([NH:19][C:20]3[S:24][C:23]([C:25]([O:27][CH3:28])=[O:26])=[C:22]([O:29][C@@H:30]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=4[C:38]([F:41])([F:39])[F:40])[CH3:31])[CH:21]=3)[CH:3]=2)[CH2:13][CH2:14]1

Komponenten

5

Edukt 3

HCID 14797Potassium HydroxideHCID 25111423(R)-Methyl 5-amino-3-(1-(2-(trifluoromethyl)phenyl)ethoxy)thiophene-2-carboxylateHCID 575389431-(3-Fluoro-4-nitrobenzyl)-4-methylpiperazine

Produkt 1

HCID 44185548(R)-Methyl 5-((5-((4-methylpiperazin-1-yl)methyl)-2-nitrophenyl)amino)-3-(1-(2-(trifluoromethyl)phenyl)ethoxy)thiophene-2-carboxylateAusbeute 50,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel2×

Versuchsvorschrift

A solution of 1-[(3-fluoro-4-nitrophenyl)methyl]-4-methylpiperazine (0.733 g, 2.90 mmol) in acetonitrile (5 mL) was added dropwise to a mixture of methyl 5-amino-3-({(1R)-1-[2-(trifluoromethyl)phenyl]ethyl}oxy)-2-thiophenecarboxylate (1.00 g, 2.90 mmol) and KOH (0.325 g, 5.79 mmol) in acetonitrile (10 mL) at 0° C. The reaction mixture was allowed to warm to room temperature overnight and then heated to 40° C. for 1 h until analysis by HPLC showed complete consumption of starting materials. The reaction mixture was partitioned between EtOAc (50 mL) and H2O (50 mL). The organic layer was washed with saturated aqueous NaHCO3 (10 mL), concentrated under reduced pressure and then purified by flash column chromatography (DCM:MeOH 98:2 to 85:15, then EtOAC:MeOH 99:1 to 85:15) to give the title compound (0.85 g, 50%) as a red amorphous solid.

Aufarbeitung

  1. temperatureheated to 40° C. for 1 h until analysis by HPLC
  2. customconsumption of starting materials
  3. customThe reaction mixture was partitioned between EtOAc (50 mL) and H2O (50 mL)
  4. washThe organic layer was washed with saturated aqueous NaHCO3 (10 mL)
  5. concentrationconcentrated under reduced pressure
  6. custompurified by flash column chromatography (DCM:MeOH 98:2 to 85:15

Quellen und Nachweise

ORD-Eintrag
ord-e2412f1094ed471c8274443eb6654c78
Quelldatensatz
uspto-grants-2012_08
Patentnummer
US08236954B2

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