Sodium Carbonate → 1-(5-(3-Aminoisoquinolin-7-yl)-4-methylpyridin-2-yl)-2,2,2-trifluoroethanol

HRID 1502459ノート

反応式

HRID 1502459 の反応式
CC1(C)C(C)(C)OB([C:9]2[CH:18]=[C:17]3[C:12]([CH:13]=[C:14]([NH2:19])[N:15]=[CH:16]3)=[CH:11][CH:10]=2)O1.Br[C:22]1[C:23]([CH3:34])=[CH:24][C:25]([CH:28]([OH:33])[C:29]([F:32])([F:31])[F:30])=[N:26][CH:27]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.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>[NH2:19][C:14]1[N:15]=[CH:16][C:17]2[C:12]([CH:13]=1)=[CH:11][CH:10]=[C:9]([C:22]1[C:23]([CH3:34])=[CH:24][C:25]([CH:28]([OH:33])[C:29]([F:31])([F:30])[F:32])=[N:26][CH:27]=1)[CH:18]=2

参加物

7

反応物 3

HCID 10340Sodium CarbonateHCID 679747981-(5-Bromo-4-methylpyridin-2-yl)-2,2,2-trifluoroethanolHCID 679762687-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-3-amine

生成物 1

HCID 679767181-(5-(3-Aminoisoquinolin-7-yl)-4-methylpyridin-2-yl)-2,2,2-trifluoroethanol収率 77.2%

試薬・触媒・溶媒 3

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

反応条件

温度
130 °C

実験手順

A mixture of 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-3-amine (225 mg, 0.583 mmol), 1-(5-bromo-4-methyl-2-pyridyl)-2,2,2-trifluoro-ethanol (200 mg, 0.741 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (41 mg, 0.06 mmol) and saturated aqueous sodium carbonate solution (0.3 mL) in acetonitrile (3 mL) was heated under microwave irradiation (Biotage) at 130° C. for 30 minutes. The reaction mixture was diluted with ethyl acetate (30 mL) and washed with water (15 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 (4 g, Silica, 0-100% ethyl acetate in heptane). Desired fractions were combined and evaporated in vacuo to afford the title compound as yellow oil (150 mg, 77%), which was used in the next step without further purification.

後処理

  1. washwashed with water (15 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 (4 g, Silica, 0-100% ethyl acetate in heptane)
  8. customevaporated in vacuo

出典と根拠

ORDレコード
ord-d048fbf835084dc1b05878452b213d7a
出典データセット
uspto-grants-2015_12
特許番号
US09206175B2

反応ノート

読み込み中…