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

HRID 468942노트

반응식

HRID 468942 반응식
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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)촉매HCID 6342Acetonitrile용매HCID 8857Ethyl Acetate용매

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온도
130 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-d6a81ff07d1743afa8662c916218f1a5
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08623889B2

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