1,2-Dibromoethane → 7-Bromo-2-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one

HRID 1987921Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1987921
[Br:1][C:2]1[CH:3]=[C:4]([C:7]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:18]([OH:21])([CH3:20])[CH3:19])=[C:12]([O:22][CH3:23])[CH:11]=2)=[O:8])[NH:5][CH:6]=1.Br[CH2:25][CH2:26]Br.[OH-].[Na+]>ClC(Cl)C.CCOC(C)=O>[Br:1][C:2]1[CH:3]=[C:4]2[C:7](=[O:8])[N:9]([C:10]3[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:18]([OH:21])([CH3:19])[CH3:20])=[C:12]([O:22][CH3:23])[CH:11]=3)[CH2:26][CH2:25][N:5]2[CH:6]=1

Komponenten

6

Edukt 3

HCID 78391,2-DibromoethaneHCID 14798Sodium HydroxideHCID 672152534-Bromo-N-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-1H-pyrrole-2-carboxamide

Produkt 1

HCID 672154747-Bromo-2-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-oneAusbeute 40,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 63651,1-DichloroethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

A mixture of 4-bromo-N-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-1H-pyrrole-2-carboxamide (1.50 g, 3.92 mmol), 1,2-dibromoethane (1.68 mL, 19.6 mmol), NBu4Br (1.26 g, 3.93 mmol) and 1N NaOH (19.6 mL, 19.6 mmol) in dichloroethane (19.6 mL) was allowed to stir at 50° C. for 16 h. The reaction mixture was cooled to rt, diluted with EtOAc (150 mL), washed with water, brine, dried over anhydrous Na2SO4 and concentrated. To the resulting brown oil was triturated with EtOAc (25 mL) to give 643 mg of the title compound as a light gray solid: 1H NMR (500 MHz, CDCl3) δ 1.34 (s, 6H), 2.67 (br. s., 1H), 3.83 (s, 2H), 3.85 (s, 3H), 4.04-4.08 (m, 2H), 4.22-4.26 (m, 2H), 6.78 (t, J=5.5 Hz, 2H), 6.90-6.95 (m, 2H), 6.99 (s, 1H); HPLC a) column: Phenomenex Luna 5μ 4.6×50 mm, 4 min gradient, 10% MeOH/90% H2O/0.1% H3PO4 to 90% MeOH/10% H2O/0.1% H3PO4; 1 min hold, 4 mL/min UV detection at 220 nm, 2.730 min retention time, (99%); HPLC b) column: Phenomenex Luna C18 4.6×50 mm, 4 min gradient, 10% MeOH/90% H2O/0.1% TFA to 90% MeOH/10% H2O/0.1% TFA, 1 min hold; 4 mL/min, UV detection at 220 nm, 2.748 min retention time; MS (ES) 409 [M+H]+

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to rt
  2. washwashed with water, brine
  3. dry with materialdried over anhydrous Na2SO4
  4. concentrationconcentrated
  5. customTo the resulting brown oil was triturated with EtOAc (25 mL)

Quellen und Nachweise

ORD-Eintrag
ord-723464fdea8741de8b44b672a62dc570
Quelldatensatz
uspto-grants-2009_06
Patentnummer
US07553836B2

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