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 81355노트

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HRID 81355 반응식
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]

참가 물질

9

반응물 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

생성물 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

시약·촉매·용매 4

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매HCID 6342Acetonitrile용매HCID 13387N-methyl-2-pyrrolidone용매

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온도
150 °C

실험 절차

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)

후처리

  1. custompurified by preparative HPLC

출처 및 근거

ORD 기록
ord-20943953e03d445aab920ef6e333b89c
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846689B2

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