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

HRID 81355ノート

反応式

HRID 81355 の反応式
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]

参加物

9

反応物 4

HCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 585225547-(2,5-Dichloro-pyrimidin-4-yloxy)-2-methyl-2,3-dihydro-isoindol-1-oneHCID 58522567Benzyl 4-amino-2-chloro-5-methoxy-benzoate

生成物 1

HCID 58522534benzyl 2-chloro-4-[5-chloro-4-(2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yloxy)-pyrimidin-2-ylamino]-5-methoxy-benzoate

試薬・触媒・溶媒 4

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 1140Toluene溶媒HCID 6342Acetonitrile溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
150 °C

実験手順

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)

後処理

  1. custompurified by preparative HPLC

出典と根拠

ORDレコード
ord-20943953e03d445aab920ef6e333b89c
出典データセット
uspto-grants-2014_09
特許番号
US08846689B2

反応ノート

読み込み中…