Potassium Phosphate, Tribasic → 1-(4-(2-Isopropyl-1-oxoisoindolin-5-yl)benzyl)-3-methylimidazolidine-2,4-dione

HRID 1891262노트

반응식

HRID 1891262 반응식
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[N:6]([CH:12]([CH3:14])[CH3:13])[CH2:5]2.[CH3:15][N:16]1[C:20](=[O:21])[CH2:19][N:18]([CH2:22][C:23]2[CH:28]=[CH:27][C:26](B3OC(C)(C)C(C)(C)O3)=[CH:25][CH:24]=2)[C:17]1=[O:38].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C(Cl)(Cl)Cl.[Pd].[Pd].C(Cl)Cl>[CH:12]([N:6]1[CH2:5][C:4]2[C:8](=[CH:9][CH:10]=[C:2]([C:26]3[CH:27]=[CH:28][C:23]([CH2:22][N:18]4[CH2:19][C:20](=[O:21])[N:16]([CH3:15])[C:17]4=[O:38])=[CH:24][CH:25]=3)[CH:3]=2)[C:7]1=[O:11])([CH3:14])[CH3:13]

참가 물질

9

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 117086345-Bromo-2-isopropylisoindolin-1-oneHCID 671722823-Methyl-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl]imidazolidine-2,4-dione

생성물 1

HCID 529320281-(4-(2-Isopropyl-1-oxoisoindolin-5-yl)benzyl)-3-methylimidazolidine-2,4-dione수율 31.2%

시약·촉매·용매 4

HCID 86615680Dipalladium chloroform촉매HCID 962Water용매2회HCID 6344Dichloromethane용매HCID 312751,4-Dioxane용매

실험 절차

5-bromo-2-isopropylisoindolin-1-one (4A4) (0.418 mmol, 106 mg) was mixed with 3-methyl-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)imidazolidine-2,4-dione (4E1) (0.418 mmol, 138 mg), tricyclohexylphosphine (0.050 mmol, 14 mg), tris(dibenzylidineacetone) dipalladium chloroform adduct (0.021 mmol, 22 mg) and potassium phosphate (0.710 mmol, 151 mg) in dioxane (2 ml) and water (1 ml). The mixture was heated to 130° C. for 15 minutes in the microwave before addition of DCM (2 ml) and water (2 ml). The reaction was stirred vigorously for 30 minutes before collection of the organic layer using a hydrophobic fritted tube followed by concentration. Purification was achieved using basic HPLC and the desired fractions concentrated to give 1-(4-(2-isopropyl-1-oxoisoindolin-5-yl)benzyl)-3-methylimidazolidine-2,4-dione (Example 4a) 49.2 mg (31.2%); 1H NMR (400 MHz, CDCl3) δ 7.91 (d, 1H) 7.67-7.59 (m, 4H) 7.37 (d, 2H) 4.7 (sept, 1H) 4.62 (s, 2H) 4.4 (s, 2H) 3.79 (s, 2H) 3.07 (s, 3H) 1.31 (d, 6H) LCMS m/z (M+H) 378.2.

후처리

  1. concentrationfollowed by concentration
  2. customPurification
  3. concentrationthe desired fractions concentrated

출처 및 근거

ORD 기록
ord-fafb9362cb0247ac9ef2e137cf126f6b
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08507521B2

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