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

HRID 1502459Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1502459
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

Komponenten

7

Edukt 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

Produkt 1

HCID 679767181-(5-(3-Aminoisoquinolin-7-yl)-4-methylpyridin-2-yl)-2,2,2-trifluoroethanolAusbeute 77,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)KatalysatorHCID 6342AcetonitrileLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
130 °C

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-d048fbf835084dc1b05878452b213d7a
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09206175B2

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