5-Bromo-4-fluoro-2-iodotoluene → N-(7-(4-bromo-5-fluoro-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide

HRID 468965

反応式

HRID 468965 の反応式
CC1(C)C(C)(C)OB([C:9]2[CH:18]=[C:17]3[C:12]([CH:13]=[C:14]([NH:19][C:20]([CH:22]4[CH2:24][CH2:23]4)=[O:21])[N:15]=[CH:16]3)=[CH:11][CH:10]=2)O1.[Br:26][C:27]1[CH:32]=[C:31]([CH3:33])[C:30](I)=[CH:29][C:28]=1[F:35]>C(#N)C.C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[Br:26][C:27]1[C:28]([F:35])=[CH:29][C:30]([C:9]2[CH:18]=[C:17]3[C:12]([CH:13]=[C:14]([NH:19][C:20]([CH:22]4[CH2:23][CH2:24]4)=[O:21])[N:15]=[CH:16]3)=[CH:11][CH:10]=2)=[C:31]([CH3:33])[CH:32]=1

参加物

7

反応物 2

HCID 121872165-Bromo-4-fluoro-2-iodotolueneHCID 67976378N-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-3-yl)cyclopropanecarboxamide

生成物 1

HCID 67974845N-(7-(4-bromo-5-fluoro-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide収率 65%

試薬・触媒・溶媒 4

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)触媒HCID 6342Acetonitrile溶媒HCID 8857Ethyl Acetate溶媒HCID 10340Sodium Carbonate溶媒

反応条件

温度
120 °C

実験手順

A mixture of N-[7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-isoquinolyl]cyclopropanecarboxamide (500 mg, 1.48 mmol), 1-bromo-2-fluoro-4-iodo-5-methyl-benzene (559 mg, 1.77 mmol), and bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (105 mg, 0.15 mmol) in ACN (6 mL) and saturated aqueous sodium carbonate (1 mL) was heated under microwave irradiation (Biotage) 120° C. for 20 minutes. The reaction mixture was diluted with ethyl acetate (50 mL) and washed with water (50 mL). The organic layer was separated, dried over sodium sulfate, filtered and concentrated in vacuo to provide a residue that was purified by flash chromatography (12 g, Silica, 0-60% ethyl acetate in heptane). Desired fractions were combined and evaporated in vacuo to afford the title compound as a white solid (385, 65%), which was used in the next step without further purification.

後処理

  1. washwashed with water (50 mL)
  2. customThe organic layer was separated
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto provide a residue that
  7. customwas purified by flash chromatography (12 g, Silica, 0-60% ethyl acetate in heptane)
  8. customevaporated in vacuo

出典と根拠

ORDレコード
ord-bcd2577d65524a3ea2ddc064afe20b68
出典データセット
uspto-grants-2014_01
特許番号
US08623889B2

関連ノート

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