Triethylamine → N-(1-bromoisoquinolin-3-yl)-1-(4-methoxyphenyl)cyclopropanecarboxamide

HRID 1471832

Reaktionsgleichung

Reaktionsgleichung von HRID 1471832
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2([C:12]([OH:14])=O)[CH2:11][CH2:10]2)=[CH:5][CH:4]=1.S(Cl)(Cl)=O.[Br:19][C:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:23]=[C:22]([NH2:30])[N:21]=1.CCN(CC)CC>C(Cl)Cl.CN(C=O)C>[Br:19][C:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:23]=[C:22]([NH:30][C:12]([C:9]2([C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=3)[CH2:10][CH2:11]2)=[O:14])[N:21]=1

Komponenten

7

Edukt 4

HCID 8471TriethylamineHCID 24386Thionyl Chloride2×HCID 855751-(4-Methoxyphenyl)cyclopropane-1-carboxylic acidHCID 2898451-Bromoisoquinolin-3-amine

Produkt 1

HCID 57733030N-(1-bromoisoquinolin-3-yl)-1-(4-methoxyphenyl)cyclopropanecarboxamideAusbeute 75 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittel2×HCID 6344DichloromethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

To 1-(4-methoxyphenyl)cyclopropanecarboxylic acid (4.07 g, 21.17 mmol), thionyl chloride (4.64 mL, 63.52 mmol) and DMF (64 μL) were stirred at 50° C. for 3 hours, after which additional thionyl chloride (4 mL) and DMF (60 μL) were added and the mixture was stirred at 50° C. for 1 additional hour. The excess thionyl chloride was evaporated under reduced pressure. The resulting acid chloride was dissolved in anhydrous DCM (20 mL) and was slowly added to a cooled suspension of (0° C.) of 1-bromoisoquinolin-3-amine in DCM (50 mL) and Et3N (14.05 mL, 100.8 mmol). The reaction mixture was stirred at room temperature for 18 hours. The resulting mixture was diluted with DCM and washed with water (1×30 mL), 1 N NaOH (2×30 mL), 1 N HCl (1×30 mL), saturated aqueous NaHCO3 (1×30 mL) and brine (1×30 mL). The organic layer was dried over anhydrous Na2SO4 and evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel (0-50% ethyl acetate in hexane) to yield N-(1-bromoisoquinolin-3-yl)-1-(4-methoxyphenyl)cyclopropanecarboxamide (6.0 g, 75%) as a yellow solid. ESI-MS m/z calc. 396.05. found 397.3 (M+1)+. Retention time 2.24 minutes. 1H NMR (400.0 MHz, CDCl3) d 8.55 (s, 1H), 8.15 (d, J=8.5 Hz, 1H), 7.89 (s, 1H), 7.78 (d, J=8.2 Hz, 1H), 7.69-7.65 (m, 1H), 7.56-7.52 (m, 1H), 7.46-7.42 (m, 2H), 7.01-6.98 (m, 2H), 3.90 (s, 3H), 1.75 (dd, J=3.7, 6.8 Hz, 2H) and 1.21 (dd, J=3.7, 6.9 Hz, 2H) ppm.

Aufarbeitung

  1. customThe excess thionyl chloride was evaporated under reduced pressure
  2. dissolutionThe resulting acid chloride was dissolved in anhydrous DCM (20 mL)
  3. stirringThe reaction mixture was stirred at room temperature for 18 hours
  4. washwashed with water (1×30 mL), 1 N NaOH (2×30 mL), 1 N HCl (1×30 mL), saturated aqueous NaHCO3 (1×30 mL) and brine (1×30 mL)
  5. dry with materialThe organic layer was dried over anhydrous Na2SO4
  6. customevaporated under reduced pressure
  7. customThe crude product was purified by column chromatography on silica gel (0-50% ethyl acetate in hexane)

Quellen und Nachweise

ORD-Eintrag
ord-03782f20a7b24980b3345bd77c4cff2c
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US09012473B2

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