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Potassium Carbonate → N-Cyclopropyl-3-fluoro-5-(4-formyl-2-(3-hydroxy-2,2-dimethylpropyl)-1-oxo-1,2-dihydroisoquinolin-6-yl)-4-methylbenzamide

HRID 906406
ノート
印刷プレビュー

反応式

HRID 906406 の反応式
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH2:13][C:14]([CH3:18])([CH3:17])[CH2:15]Cl)[CH:6]=[C:5]2[CH:19]=[O:20].C([O-])(=[O:23])C.[K+].[CH:26]1([NH:29][C:30](=[O:48])[C:31]2[CH:36]=[C:35](B3OC(C)(C)C(C)(C)O3)[C:34]([CH3:46])=[C:33]([F:47])[CH:32]=2)[CH2:28][CH2:27]1.C(=O)([O-])[O-].[K+].[K+]>CN1C(=O)CCC1.O.CO>[CH:26]1([NH:29][C:30](=[O:48])[C:31]2[CH:36]=[C:35]([C:2]3[CH:3]=[C:4]4[C:9](=[CH:10][CH:11]=3)[C:8](=[O:12])[N:7]([CH2:13][C:14]([CH3:18])([CH3:17])[CH2:15][OH:23])[CH:6]=[C:5]4[CH:19]=[O:20])[C:34]([CH3:46])=[C:33]([F:47])[CH:32]=2)[CH2:27][CH2:28]1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

8

反応物 4

HCID 11430Potassium CarbonateHCID 517044Potassium AcetateHCID 21914563N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamideHCID 866409616-Bromo-2-(3-chloro-2,2-dimethylpropyl)-1-oxo-1,2-dihydroisoquinoline-4-carbaldehyde

生成物 1

HCID 86640963N-Cyclopropyl-3-fluoro-5-(4-formyl-2-(3-hydroxy-2,2-dimethylpropyl)-1-oxo-1,2-dihydroisoquinolin-6-yl)-4-methylbenzamide
収率 87.1%

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 962Water溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
130 °C

実験手順

A solution of 6-bromo-2-(3-chloro-2,2-dimethylpropyl)-1-oxo-1,2-dihydroisoquinoline-4-carbaldehyde (Example 2b, 0.50 g) dissolved in NMP (5 mL) was treated with potassium acetate (0.17 g) under nitrogen. The resulting mixture was stirred at 130° C. for 20 h. The mixture was then treated with N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (0.63 g), Pd-118 (0.046 g) and potassium carbonate (0.43 g) under nitrogen and stirred at 80° C. for 4 h. After cooling to room temperature methanol (10 mL) was added and the mixture stirred for 1 h. The reaction mixture was diluted with water (250 mL), and extracted with ethyl acetate (250 mL). The organic was dried (MgSO4), filtered and evaporated to afford crude product. The crude product was purified (SiO2 chromatography, elution with 100% ethyl acetate) to afford the subtitle compound (0.55 g) as an oil.

後処理

  1. stirringstirred at 80° C. for 4 h
  2. additionwas added
  3. stirringthe mixture stirred for 1 h
  4. extractionextracted with ethyl acetate (250 mL)
  5. dry with materialThe organic was dried (MgSO4)
  6. filtrationfiltered
  7. customevaporated
  8. customto afford crude product
  9. customThe crude product was purified
  10. wash(SiO2 chromatography, elution with 100% ethyl acetate)

出典と根拠

ORDレコード
ord-871a6180d7ff4f97925a12c12c54b153
出典データセット
uspto-grants-2011_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08012980B2

反応ノート

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