Potassium Phosphate, Tribasic → 3-Cyclopropyl-1-(4-(2-cyclopropyl-1-oxoisoindolin-5-yl)benzyl)imidazolidine-2,4-dione

HRID 1891270ノート

反応式

HRID 1891270 の反応式
Br[C:2]1[CH:18]=[CH:17][C:5]([CH2:6][N:7]2[CH2:11][C:10](=[O:12])[N:9]([CH:13]3[CH2:15][CH2:14]3)[C:8]2=[O:16])=[CH:4][CH:3]=1.[CH:19]1([N:22]2[CH2:30][C:29]3[C:24](=[CH:25][CH:26]=[C:27](B4OC(C)(C)C(C)(C)O4)[CH:28]=3)[C:23]2=[O:40])[CH2:21][CH2:20]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O>[CH:13]1([N:9]2[C:10](=[O:12])[CH2:11][N:7]([CH2:6][C:5]3[CH:17]=[CH:18][C:2]([C:27]4[CH:28]=[C:29]5[C:24](=[CH:25][CH:26]=4)[C:23](=[O:40])[N:22]([CH:19]4[CH2:21][CH2:20]4)[CH2:30]5)=[CH:3][CH:4]=3)[C:8]2=[O:16])[CH2:15][CH2:14]1

参加物

7

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 594023502-Cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-oneHCID 66813314HCID 66813314、化合物

生成物 1

HCID 529323943-Cyclopropyl-1-(4-(2-cyclopropyl-1-oxoisoindolin-5-yl)benzyl)imidazolidine-2,4-dione収率 53.1%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

実験手順

1-(4-bromobenzyl)-3-cyclopropylimidazolidine-2,4-dione (7H5) (0.1 mmol, 30 mg), 2-cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-one (1A5) (0.1 mmol, 31.0 mg), tris(dibenzylidineacetone)dipalladium (0.005 mmol, 4.59 mg), tricyclohexylphosphine (0.012 mmol, 3.37 mg) and potassium phosphate (0.17 mmol, 36.1 mg) were suspended in dioxane (1 ml) and water (0.5 ml) and heated to 130° C. in the microwave for 15 min. The reaction mixture was quenched with 2 ml of water and 3 ml of DCM and the organic phase separated using a hydrophobic fritted tube. The organic phase was concentrated and the residue purified by prep basic HPLC to give 3-cyclopropyl-1-(4-(2-cyclopropyl-1-oxoisoindolin-5-yl)benzyl)imidazolidine-2,4-dione (Example 7a) 21.3 mg (53%); 1H NMR (400 MHz, CDCl3) δ 7.88 (d, 1H) 7.63 (d, 1H) 7.58 (m, 3H) 7.35 (d, 2H) 4.59 (s, 2H) 4.37 (s, 2H) 3.71 (s, 2H) 2.96 (m, 1H) 2.64 (m, 1H) 1.01-0.86 (m, 8H) LCMS m/z (M+H) 402.2.

後処理

  1. customThe reaction mixture was quenched with 2 ml of water and 3 ml of DCM
  2. customthe organic phase separated
  3. concentrationThe organic phase was concentrated
  4. customthe residue purified by prep basic HPLC

出典と根拠

ORDレコード
ord-d1226a04fb9d4fe4a3c674fdb3500300
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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