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

HRID 1891262ノート

反応式

HRID 1891262 の反応式
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]

参加物

9

反応物 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

生成物 1

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

試薬・触媒・溶媒 4

HCID 86615680Dipalladium chloroform触媒HCID 962Water溶媒2 回HCID 6344Dichloromethane溶媒HCID 312751,4-Dioxane溶媒

実験手順

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.

後処理

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

出典と根拠

ORDレコード
ord-fafb9362cb0247ac9ef2e137cf126f6b
出典データセット
uspto-grants-2013_08
特許番号
US08507521B2

反応ノート

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