Dichloromethane → (R)-Methyl 3-methyl-2-(1-oxo-5-(4-(3-(3-(trifluoromethyl)phenyl)ureido)phenyl)isoindolin-2-yl)butanoate

HRID 403955

반응식

HRID 403955 반응식
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[N:6]([C@H:12]([CH:17]([CH3:19])[CH3:18])[C:13]([O:15][CH3:16])=[O:14])[CH2:5]2.CC1(C)C(C)(C)OB([C:28]2[CH:33]=[CH:32][C:31]([NH:34][C:35]([NH:37][C:38]3[CH:43]=[CH:42][CH:41]=[C:40]([C:44]([F:47])([F:46])[F:45])[CH:39]=3)=[O:36])=[CH:30][CH:29]=2)O1.C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[CH3:18][CH:17]([CH3:19])[C@@H:12]([N:6]1[CH2:5][C:4]2[C:8](=[CH:9][CH:10]=[C:2]([C:28]3[CH:29]=[CH:30][C:31]([NH:34][C:35]([NH:37][C:38]4[CH:43]=[CH:42][CH:41]=[C:40]([C:44]([F:45])([F:46])[F:47])[CH:39]=4)=[O:36])=[CH:32][CH:33]=3)[CH:3]=2)[C:7]1=[O:11])[C:13]([O:15][CH3:16])=[O:14]

참가 물질

8

반응물 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 161251031-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-3-(3-(trifluoromethyl)phenyl)ureaHCID 86673568(R)-Methyl 2-(5-bromo-1-oxoisoindolin-2-yl)-3-methylbutanoate

생성물 1

HCID 131731536(R)-Methyl 3-methyl-2-(1-oxo-5-(4-(3-(3-(trifluoromethyl)phenyl)ureido)phenyl)isoindolin-2-yl)butanoate

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 6228Dimethylformamide용매

반응 조건

온도
82.5 °C

실험 절차

The compound of example 359 (288 mg, 0.886 mmol), compound of example 357 (300 mg, 0.738 mmol) and Pd(dppf)Cl2: CH2Cl2 (18 mg, 0.022 mmol) were taken in DMF (5 mL) under an argon atmosphere. To this reaction mixture, 2M solution of Na2CO3 (234 mg, 2.214 mmol, 1.1 mL) was added and the reaction mixture was stirred at 80-85° C. for 1 to 1.5 h. After completion of the reaction, water was added to the reaction mixture and the product obtained was extracted with ether. The combined ether layers were washed with water and brine, dried over anhydrous Na2SO4 or MgSO4. The solvent was evaporated and the product was purified by column chromatography (silica gel, 30% ethyl acetate in petroleum ether) to obtain the title compound.

후처리

  1. additionwas added to the reaction mixture
  2. customthe product obtained
  3. extractionwas extracted with ether
  4. washThe combined ether layers were washed with water and brine
  5. dry with materialdried over anhydrous Na2SO4 or MgSO4
  6. customThe solvent was evaporated
  7. customthe product was purified by column chromatography (silica gel, 30% ethyl acetate in petroleum ether)

출처 및 근거

ORD 기록
ord-6fe32822517e4cbaafc362f966cf49cd
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08748426B2

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