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

HRID 883572Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 883572
Br[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.C([O-])([O-])=O.[Cs+].[Cs+].C>O1CCOCC1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CCCCCCC>[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

8

Edukt 4

HCID 297MethaneHCID 10796Cesium carbonateHCID 25111423(R)-Methyl 5-amino-3-(1-(2-(trifluoromethyl)phenyl)ethoxy)thiophene-2-carboxylateHCID 441854911-(3-Bromo-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 70 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)KatalysatorHCID 8900HeptaneLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
55 °C

Versuchsvorschrift

A mixture of 1-[(3-bromo-4-nitrophenyl)methyl]-4-methylpiperazine (0.675 g, 2.15 mmol), methyl 5-amino-3-({(1R)-1-[2-(trifluoromethyl)phenyl]ethyl}oxy)-2-thiophenecarboxylate (0.794 g, 2.30 mmol), Cs2CO3 (3.50 g, 10.7 mmol), XANTPHOS (0.053 g, 0.088 mmol) and tris(benzylideneacetone)dipalladium(0) (0.039 g, 0.043 mmol) in dioxane (5.4 mL) was heated to 55° C. for 1.5 h, analysed by HPLC, then cooled to room temperature. Heptane (2.4 mL), charcoal (0.27 g) and celite (0.27 g) were added. The suspension was stirred for 30 min at room temperature, and then filtered over celite, rinsing with toluene (13.5 mL×3). The filtrate was concentrated under reduced pressure and purified by flash column chromatography (DCM:MeOH:NEt3 9:1:0.1) to give the title compound (0.867 g, 70%) as a red amorphous solid.

Aufarbeitung

  1. temperatureby HPLC, then cooled to room temperature
  2. filtrationfiltered over celite
  3. washrinsing with toluene (13.5 mL×3)
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. custompurified by flash column chromatography (DCM:MeOH:NEt3 9:1:0.1)

Quellen und Nachweise

ORD-Eintrag
ord-203c886be18c4adca8ac5a160f9338af
Quelldatensatz
uspto-grants-2012_08
Patentnummer
US08236954B2

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