Acetamide → [6-[[1-[[4-(4-Morpholinyl)-3-(trifluoromethyl)phenylamino]carbonyl]-1H-indol-5-yl]oxy]-4-pyrimidinyl]acetamide

HRID 2264607Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2264607
Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([O:8][C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[N:14]([C:18]([NH:20][C:21]2[CH:26]=[CH:25][C:24]([N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[C:23]([C:33]([F:36])([F:35])[F:34])[CH:22]=2)=[O:19])[CH2:13][CH2:12]3)[CH:3]=1.[C:37]([NH2:40])(=[O:39])[CH3:38].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.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]>[N:27]1([C:24]2[CH:25]=[CH:26][C:21]([NH:20][C:18]([N:14]3[C:15]4[C:11](=[CH:10][C:9]([O:8][C:4]5[N:5]=[CH:6][N:7]=[C:2]([CH2:38][C:37]([NH2:40])=[O:39])[CH:3]=5)=[CH:17][CH:16]=4)[CH:12]=[CH:13]3)=[O:19])=[CH:22][C:23]=2[C:33]([F:35])([F:36])[F:34])[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1

Komponenten

7

Edukt 4

HCID 178AcetamideHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 866182902,3-dihydro-5-(6-chloro-4-pyrimidinyloxy)-N-[4-(4-morpholinyl)-3-(trifluoromethyl)phenyl]-1H-indole-1-carboxamide

Produkt 1

HCID 67531453[6-[[1-[[4-(4-Morpholinyl)-3-(trifluoromethyl)phenylamino]carbonyl]-1H-indol-5-yl]oxy]-4-pyrimidinyl]acetamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

A mixture of 2,3-dihydro-5-(6-chloro-4-pyrimidinyloxy)-N-[4-(4-morpholinyl)-3-(trifluoromethyl)phenyl]-1H-indole-1-carboxamide (Intermediate IIa; 1.30 g, 2.5 mmol), acetamide (0.22 g, 3.75 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis[diphenylphosphine] (90 mg, 0.15 mmol), tris(dibenzylideneacetone)dipalladium (45 mg, 0.05 mmol), caesium carbonate (1.14 g, 3.5 mmol) in dry dioxan (10 mL) is heated under an argon atmosphere at 70° C. for 15 h. The cooled suspension is filtered and the residue is dissolved in DMF (50 mL). The resulting solution is filtered (hyflo) and the solvent is evaporated off under reduced pressure to afford the crude product which is purified by preparative HPLC (VP Reprosil 100 Å-5 μm; eluent 0.1% TFA/H2O→0.09% TFA/CH3CN) and neutralised with saturated aqueous NaHCO3 to give the title compound as a colourless crystalline solid, m.p. 272-275° C.

Aufarbeitung

  1. filtrationThe cooled suspension is filtered
  2. dissolutionthe residue is dissolved in DMF (50 mL)
  3. filtrationThe resulting solution is filtered (hyflo)
  4. customthe solvent is evaporated off under reduced pressure
  5. customto afford the crude product which
  6. customis purified by preparative HPLC (VP Reprosil 100 Å-5 μm; eluent 0.1% TFA/H2O→0.09% TFA/CH3CN)

Quellen und Nachweise

ORD-Eintrag
ord-531bff4363e6453cb220043f494e27ab
Quelldatensatz
uspto-grants-2010_12
Patentnummer
US07855215B2

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