18-Crown-6 → N-(4-{4-amino-7-[(diphenylmethylene)amino]thieno[3,2-c]pyridin-3-yl}-2-methoxyphenyl)-1-methyl-1H-indole-2-carboxamide

HRID 17232

Reaktionsgleichung

Reaktionsgleichung von HRID 17232
[NH2:1][C:2]1[C:7]2[C:8]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]4[N:21]([CH3:29])[C:22]5[C:27]([CH:28]=4)=[CH:26][CH:25]=[CH:24][CH:23]=5)=[O:19])=[C:13]([O:30][CH3:31])[CH:12]=3)=[CH:9][S:10][C:6]=2[C:5](I)=[CH:4][N:3]=1.CC(C)([O-])C.[Na+].C1OCCOCCOCCOCCOCCOC1.[C:57](=[NH:70])([C:64]1[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=1)[C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=1>CN(C)C=O.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]>[NH2:1][C:2]1[C:7]2[C:8]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]4[N:21]([CH3:29])[C:22]5[C:27]([CH:28]=4)=[CH:26][CH:25]=[CH:24][CH:23]=5)=[O:19])=[C:13]([O:30][CH3:31])[CH:12]=3)=[CH:9][S:10][C:6]=2[C:5]([N:70]=[C:57]([C:58]2[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=2)[C:64]2[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=2)=[CH:4][N:3]=1

Komponenten

7

Edukt 4

HCID 2855718-Crown-6HCID 136809Benzophenone imineHCID 18451298N-[4-(4-amino-7-iodothieno[3,2-c]pyridin-3-yl)-2-methoxyphenyl]-1-methyl-1H-indole-2-carboxamideHCID 23676156Sodium t-butoxide

Produkt 1

HCID 18451290N-(4-{4-amino-7-[(diphenylmethylene)amino]thieno[3,2-c]pyridin-3-yl}-2-methoxyphenyl)-1-methyl-1H-indole-2-carboxamideAusbeute 64,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
95 °C

Versuchsvorschrift

A mixture of N-[4-(4-amino-7-iodothieno[3,2-c]pyridin-3-yl)-2-methoxyphenyl]-1-methyl-1H-indole-2-carboxamide (4.03 g, 7.72 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.283 g, 0.31 mmol, 9,9-dimethyl-4-5-bis(diphenylphosphino)xanthene (0.536 g, 0.93 mmol), sodium tert-butoxide (1.00 g, 10.42 mmol), 18-crown-6 (2.75 g, 10.42 mmol), and benzophenone imine (1.16 mL, 6.9 mmol) were combined in N,N-dimethylformamide (100 mL), and the solution was heated at 95° C. for 12 h. The reaction mixture was cooled to ambient temperature and concentrated. The residue was diluted with brine (100 mL) and extracted with methanol/dichloromethane (1:33, 3×150 mL). The organic layers were combined, dried over magnesium sulfate, filtered, and concentrated. Purification of the residue by flash column chromatography on silica gel which had been deactivated with triethylamine (10% by volume of silica gel used), using a gradient of ethyl acetate/heptane (1:3 to 4:1) as the mobile phase afforded the title compound (2.71 g, 4.47 mmol) as a yellow foam: MS: (MH)+ 608; LCMS (Conditions a), Rt 2.27 min.

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. concentrationconcentrated
  3. additionThe residue was diluted with brine (100 mL)
  4. extractionextracted with methanol/dichloromethane (1:33, 3×150 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification of the residue by flash column chromatography on silica gel which

Quellen und Nachweise

ORD-Eintrag
ord-519bff0f3f7642d895ebf6ca62703d8f
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07737160B2

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