2-(Propane-2-sulfonyl)aniline → Methyl 4'-(5-chloro-4-(2-(isopropylsulfonyl)phenylamino)pyridin-2-ylamino)-5'-methoxy-2'-methylbiphenyl-4-carboxylate

HRID 1664689

Reaktionsgleichung

Reaktionsgleichung von HRID 1664689
Br[C:2]1[C:7]([Cl:8])=[CH:6][N:5]=[C:4]([NH:9][C:10]2[C:15]([O:16][CH3:17])=[CH:14][C:13]([C:18]3[CH:23]=[CH:22][C:21]([C:24]([O:26][CH3:27])=[O:25])=[CH:20][CH:19]=3)=[C:12]([CH3:28])[CH:11]=2)[CH:3]=1.[CH:29]([S:32]([C:35]1[CH:41]=[CH:40][CH:39]=[CH:38][C:36]=1[NH2:37])(=[O:34])=[O:33])([CH3:31])[CH3:30].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(CCC)=CC(CCC)=CC=2CCC)CCCCC1.CC(C)([O-])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1COCC1>[Cl:8][C:7]1[C:2]([NH:37][C:36]2[CH:38]=[CH:39][CH:40]=[CH:41][C:35]=2[S:32]([CH:29]([CH3:31])[CH3:30])(=[O:34])=[O:33])=[CH:3][C:4]([NH:9][C:10]2[C:15]([O:16][CH3:17])=[CH:14][C:13]([C:18]3[CH:23]=[CH:22][C:21]([C:24]([O:26][CH3:27])=[O:25])=[CH:20][CH:19]=3)=[C:12]([CH3:28])[CH:11]=2)=[N:5][CH:6]=1

Komponenten

7

Edukt 4

HCID 126463662-(Propane-2-sulfonyl)anilineHCID 21081571Dicyclohexyl(2',4',6'-tripropyl-[1,1'-biphenyl]-2-yl)phosphineHCID 23676156Sodium t-butoxideHCID 59764478Methyl 4'-(4-bromo-5-chloropyridin-2-ylamino)-5'-methoxy-2'-methylbiphenyl-4-carboxylate

Produkt 1

HCID 59764572Methyl 4'-(5-chloro-4-(2-(isopropylsulfonyl)phenylamino)pyridin-2-ylamino)-5'-methoxy-2'-methylbiphenyl-4-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

Methyl 4′-(4-bromo-5-chloropyridin-2-ylamino)-5′-methoxy-2′-methylbiphenyl-4-carboxylate generated in Step 2 (9 mg, 0.022 mmol), 2-(isopropylsulfonyl)aniline (4 mg, 0.022 mmol, 1 equiv), Pd2(dba)3 (1.7 mg, 0.002 mmol, 0.1 equiv.), 2-(Dicyclohexylphosphino)-2′,4′,6′-tri-1-propyl-1,1′-biphenyl (1.8 mg, 0.004 mmol, 0.2 equiv.), and Sodium tert-butoxide (2.7 mg, 0.028 mmol, 1.3 equiv.) are added to THF (1 mL). The resulting mixture is bubbled with N2 gas for 5 minutes and then heated at 150° C. for 4 hours. After cooling to room temperature, the reaction mixture is diluted into EtOAc and washed with H2O. The EtOAc layer is dried over Mg2SO4 and concentrated in vacuo. Silica gel chromatography (hexanes-EtOAc) affords Methyl 4′-(5-chloro-4-(2-(isopropylsulfonyl)phenylamino)pyridin-2-ylamino)-5′-methoxy-2′-methylbiphenyl-4-carboxylate (254); MS m/z 580.2 (M+1).

Aufarbeitung

  1. customThe resulting mixture is bubbled with N2 gas for 5 minutes
  2. temperatureAfter cooling to room temperature
  3. additionthe reaction mixture is diluted into EtOAc
  4. washwashed with H2O
  5. dry with materialThe EtOAc layer is dried over Mg2SO4
  6. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-830d7e361cb342fca5f70b840c7fcd68
Quelldatensatz
uspto-grants-2011_10
Patentnummer
US08039479B2

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