Water → N-(7-(5-amino-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide

HRID 468730

Reaktionsgleichung

Reaktionsgleichung von HRID 468730
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH:12][C:13]([CH:15]3[CH2:17][CH2:16]3)=[O:14])[N:8]=[CH:9]2)=[CH:4][CH:3]=1.[NH2:18][C:19]1[CH:20]=[CH:21][C:22]([CH3:34])=[C:23](B2OC(C)(C)C(C)(C)O2)[CH:24]=1.C(=O)([O-])[O-].[K+].[K+].O1CCOCC1.O.C([O-])(O)=O.[Na+]>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>[NH2:18][C:19]1[CH:24]=[CH:23][C:22]([CH3:34])=[C:21]([C:2]2[CH:11]=[C:10]3[C:5]([CH:6]=[C:7]([NH:12][C:13]([CH:15]4[CH2:17][CH2:16]4)=[O:14])[N:8]=[CH:9]3)=[CH:4][CH:3]=2)[CH:20]=1

Komponenten

8

Edukt 6

HCID 962WaterHCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 516892Sodium BicarbonateHCID 160860894-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 67974626N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide

Produkt 1

HCID 67974803N-(7-(5-amino-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamideAusbeute 119 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)Katalysator

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

To a mixture of N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide (1.053 g, 3.617 mmol), 5-amino-2-methylphenylboronic acid pinacol ester (1.2607 g, 5.4081 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (0.1311 g, 0.1852 mmol), and potassium carbonate (1.385 g, 10.02 mmol) was added 1,4-dioxane (20 mL, 200 mmol) and water (2 mL, 100 mmol). The reaction mixture was then heated at 90° C. for 2 hours and then cooled to room temperature. The reaction mixture was poured into saturated aqueous NaHCO3 and extracted twice with dichloromethane. The combined organics were dried over MgSO4, filtered, and evaporated in vacuo. The crude product was purified via flash chromatography on silica gel (40 g silica, solvent gradient: 0-80% ethyl acetate in dichloromethane) to yield 1.3653 g (119%) of N-(7-(5-amino-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide. LCMS (ESI): M+H=318.2; 1H NMR (400 MHz, DMSO-d6) δ 10.87 (s, 1H), 9.16 (s, 1H), 8.47 (s, 1H), 7.92 (s, 1H), 7.87 (d, J=8.5 Hz, 1H), 7.63 (dd, J=8.5, 1.5 Hz, 1H), 6.97 (d, J=8.8 Hz, 1H), 6.60-6.49 (m, 2H), 4.93 (s, 2H), 2.14-2.02 (m, 4H), 0.85 (dd, J=12.4, 6.1 Hz, 4H).

Aufarbeitung

  1. temperaturecooled to room temperature
  2. extractionextracted twice with dichloromethane
  3. dry with materialThe combined organics were dried over MgSO4
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customThe crude product was purified via flash chromatography on silica gel (40 g silica, solvent gradient: 0-80% ethyl acetate in dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-d52e2aa611cf4daaa4b6016be77b0155
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08623889B2

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