Cesium carbonate → N-(7-(5-methoxy-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide

HRID 1502310

Reaktionsgleichung

Reaktionsgleichung von HRID 1502310
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[CH:32]=[C:31]([O:33][CH3:34])[CH:30]=[CH:29][C:28]=1[CH3:35].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:34][O:33][C:31]1[CH:30]=[CH:29][C:28]([CH3:35])=[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)[CH:32]=1

Komponenten

6

Edukt 3

HCID 10796Cesium carbonateHCID 5202882-Bromo-4-methoxy-1-methylbenzeneHCID 67976378N-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-3-yl)cyclopropanecarboxamide

Produkt 1

HCID 68095312N-(7-(5-methoxy-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamideAusbeute 21,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 218864351,4-Dioxane--water (1/1)Lösungsmittel

Reaktionsbedingungen

Temperatur
130 °C

Versuchsvorschrift

To a solution of N-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-3-yl)cyclopropanecarboxamide (200 mg, 0.59 mmol) in dioxane/water (5.0 ml) were added 2-bromo-4-methoxy-1-methylbenzene (100 mg, 0.50 mmol), cesium carbonate (391 mg, 1.2 mmol) and [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (22 mg, 0.03 mmol). It was purged with nitrogen and heated at 130° C. for 30 min under microwave irradiation. The reaction mixture was concentrated, washed with water and extracted with ethyl acetate. It was dried over sodium sulfate, concentrated and purified by pre-HPLC to give the product (36 mg, 18.4%). LCMS (ESI): RT (Min)=1.214, M+H+=332.9, method=A; 1H NMR (400 MHz, DMSO-d6) δ 9.17 (s, 1H), 8.49 (s, 1H), 8.00 (s, 1H), 7.90 (d, J=8.8 Hz, 1H), 7.70-7.68 (m, 1H), 7.24 (d, J=8.4 Hz, 1H), 6.91-6.86 (m, 2H), 3.76 (s, 3H), 2.19 (s, 3H), 2.09-2.05 (m, 1H), 0.87-0.81 (m, 4H).

Aufarbeitung

  1. customIt was purged with nitrogen
  2. concentrationThe reaction mixture was concentrated
  3. washwashed with water
  4. extractionextracted with ethyl acetate
  5. dry with materialIt was dried over sodium sulfate
  6. concentrationconcentrated
  7. custompurified by pre-HPLC

Quellen und Nachweise

ORD-Eintrag
ord-922bcd5272aa4ce7aebd4a0bbaa32743
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09206175B2

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