Potassium Acetate → (S)-tert-Butyl 4-(1-cyano-2-(4-(1-oxoisoindolin-5-yl)phenyl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

HRID 216939ノート

反応式

HRID 216939 の反応式
[C:1]([C@@H:3]([NH:12][C:13]([C:15]1([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)=[O:14])[CH2:4][C:5]1[CH:10]=[CH:9][C:8](I)=[CH:7][CH:6]=1)#[N:2].C([O-])(=O)C.[K+].CC1(C)C(C)(C)OB([C:42]2[CH:43]=[C:44]3[C:48](=[CH:49][CH:50]=2)[C:47](=[O:51])[NH:46][CH2:45]3)O1>C(#N)C.O>[C:1]([C@@H:3]([NH:12][C:13]([C:15]1([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)=[O:14])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:42]2[CH:43]=[C:44]3[C:48](=[CH:49][CH:50]=2)[C:47](=[O:51])[NH:46][CH2:45]3)=[CH:7][CH:6]=1)#[N:2]

参加物

6

反応物 3

HCID 517044Potassium AcetateHCID 219557955-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-oneHCID 59568614(S)-tert-Butyl 4-(1-cyano-2-(4-iodophenyl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

生成物 1

HCID 59568570(S)-tert-Butyl 4-(1-cyano-2-(4-(1-oxoisoindolin-5-yl)phenyl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate収率 60.9%

試薬・触媒・溶媒 2

HCID 962Water溶媒2 回HCID 6342Acetonitrile溶媒

反応条件

温度
90 °C

実験手順

A mixture of (S)-tert-butyl 4-(1-cyano-2-(4-iodophenyl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 15, step (i), 260 mg), potassium acetate (153 mg) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-one (162 mg) in acetonitrile (10 mL) and water (5 mL) under a nitrogen atmosphere, was treated with 1,1 bis(di-tert-butylphosphino)ferrocene palladium dichloride (10 mg) and the mixture stirred and heated at 90° C. for 18 h. The reaction mixture was cooled to room temperature and diluted with water. The products were extracted into ethyl acetate (2×100 mL) and the combined extracts dried over magnesium sulphate and concentrated to dryness. The residue was purified by chromatography on silica eluting with ethyl acetate to afford the sub-titled compound (160 mg).

後処理

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionThe products were extracted into ethyl acetate (2×100 mL)
  3. dry with materialthe combined extracts dried over magnesium sulphate
  4. concentrationconcentrated to dryness
  5. customThe residue was purified by chromatography on silica eluting with ethyl acetate

出典と根拠

ORDレコード
ord-f5844caf2b42412188bd4b2d0ebfbb7c
出典データセット
uspto-grants-2012_06
特許番号
US08193239B2

反応ノート

読み込み中…