Cesium carbonate → benzyl 2-chloro-4-[5-chloro-4-(2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yloxy)-pyrimidin-2-ylamino]-5-methoxy-benzoate

Reaktionsgleichung

Cl[C:2]1[N:7]=[C:6]([O:8][C:9]2[CH:10]=[CH:11][CH:12]=[C:13]3[C:17]=2[C:16](=[O:18])[N:15]([CH3:19])[CH2:14]3)[C:5]([Cl:20])=[CH:4][N:3]=1.[NH2:21][C:22]1[C:37]([O:38][CH3:39])=[CH:36][C:25]([C:26]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[O:27])=[C:24]([Cl:40])[CH:23]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C([O-])([O-])=O.[Cs+].[Cs+]>C(#N)C.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].CN1C(=O)CCC1.C1(C)C=CC=CC=1>[Cl:40][C:24]1[CH:23]=[C:22]([NH:21][C:2]2[N:7]=[C:6]([O:8][C:9]3[CH:10]=[CH:11][CH:12]=[C:13]4[C:17]=3[C:16](=[O:18])[N:15]([CH3:19])[CH2:14]4)[C:5]([Cl:20])=[CH:4][N:3]=2)[C:37]([O:38][CH3:39])=[CH:36][C:25]=1[C:26]([O:28][CH2:29][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)=[O:27]

Komponenten

Reaktionsbedingungen

Temperatur: 150 °C

Versuchsvorschrift

7-(2,5-dichloro-pyrimidin-4-yloxy)-2-methyl-2,3-dihydro-isoindol-1-one (0.10 g), benzyl 4-amino-2-chloro-5-methoxy-benzoate (0.28 g), Pd2dba3 (18 mg), X-Phos (37 mg) and Cs2CO3 are weighed into a microwave vial and argon flushing is carried out. Then toluene (1 mL) and NMP (50 μL) are added, argon flushing is carried out again and the mixture is stirred for 5 min at 150° C. in the microwave. For working up the mixture is diluted with ACN (20 mL) and combined with Isolute (Separtis GmbH). The solvent is eliminated in vacuo and then purified by preparative HPLC. (IC50=53 nmol)

Aufarbeitung

custompurified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag: ord-20943953e03d445aab920ef6e333b89c
Quelldatensatz: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08846689B2

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