Sodium Carbonate → N-(7-(3-fluoro-2-formyl-6-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide

HRID 468968

Reaktionsgleichung

Reaktionsgleichung von HRID 468968
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[C:27]1[C:34]([CH3:35])=[CH:33][CH:32]=[C:31]([F:36])[C:28]=1[CH:29]=[O:30].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>[F:36][C:31]1[C:28]([CH:29]=[O:30])=[C:27]([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:34]([CH3:35])=[CH:33][CH:32]=1

Komponenten

7

Edukt 3

HCID 10340Sodium CarbonateHCID 190073762-Bromo-6-fluoro-3-methylbenzaldehydeHCID 67976378N-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-3-yl)cyclopropanecarboxamide

Produkt 1

HCID 86674986N-(7-(3-fluoro-2-formyl-6-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamideAusbeute 97 %

Reagenzien, Katalysatoren, Lösungsmittel 3

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

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

A mixture of N-[7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-isoquinolyl]cyclopropanecarboxamide (100 mg, 0.30 mmol), 2-bromo-6-fluoro-3-methyl-benzaldehyde (77 mg; 0.35 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (21 mg, 0.03 mmol) and saturated aqueous sodium carbonate solution (0.1 mL) in acetonitrile (1 mL) was heated under microwave irradiation (Biotage) at 120° 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, 0-60% ethyl acetate in heptane). Desired fractions were combined and evaporated in vacuo to afford the title compound as light brown solid (100 mg, 97%), 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, 0-60% ethyl acetate in heptane)
  8. customevaporated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-f086e79a2df140119f10e7d01f354ea2
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08623889B2

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