Hydrochloric Acid → 5-((4-chlorophenoxy)methyl)-2-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyridazin-3(2H)-one

HRID 2059859Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2059859
N1C=CC=CC=1.[Cl:7][C:8]1[CH:22]=[CH:21][C:11]([O:12][CH2:13][C:14]2[CH:19]=[N:18][NH:17][C:16](=[O:20])[CH:15]=2)=[CH:10][CH:9]=1.[OH:23][C:24]([CH3:39])([CH3:38])[CH2:25][O:26][C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][C:28]=1[O:36][CH3:37].Cl>C(Cl)Cl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Cl:7][C:8]1[CH:9]=[CH:10][C:11]([O:12][CH2:13][C:14]2[CH:19]=[N:18][N:17]([C:30]3[CH:31]=[CH:32][C:27]([O:26][CH2:25][C:24]([OH:23])([CH3:39])[CH3:38])=[C:28]([O:36][CH3:37])[CH:29]=3)[C:16](=[O:20])[CH:15]=2)=[CH:21][CH:22]=1

Komponenten

7

Edukt 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 585798634-(2-Hydroxy-2-methylpropoxy)-3-methoxyphenylboronic acidHCID 585798765-((4-chlorophenoxy)methyl)pyridazin-3(2H)-one

Produkt 1

HCID 469272095-((4-chlorophenoxy)methyl)-2-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyridazin-3(2H)-one

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8895Cupric acetateKatalysatorHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Pyridine (0.123 mL, 1.52 mmol) was added in portions over 4 hr to a stirred mixture of 5-((4-chlorophenoxy)methyl)pyridazin-3(2H)-one Part B (36 mg, 0.15 mmol), copper(II) acetate (91 mg, 0.46 mmol), and 4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenylboronic acid Part D of Procedure 4 (73.0 mg, 0.30 mmol) in CH2Cl2 (15 mL) at RT (flask left open to air). The mixture was poured into 3.0 N aqueous HCl (100 mL) and extracted with CH2Cl2. The CH2Cl2 layer was dried over Na2SO4 and concentrated. The crude product was purified by prep-HPLC (C18 column/H2O:MeOH:TFA 90:10:0.1 to 10:90:0.1 gradient) giving the title compound 5-((4-chlorophenoxy)methyl)-2-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyridazin-3(2H)-one E-2 (25 mg, 38% yield) as an off-white solid. LC/MS 431 (M+H)+, tR 0.93 min (method 5); 1H NMR (500 MHz, Chloroform-D) δ ppm 7.94 (1H, d, J=1.92 Hz), 7.30 (2H, d), 7.12-7.17 (2H, m), 7.09 (1H, br. s.), 6.98 (1H, d, J=8.25 Hz), 6.91 (2H, d), 4.97 (2H, s), 3.82-3.92 (5H, m), 1.35 (6H, s).

Aufarbeitung

  1. wait(flask left open to air)
  2. extractionextracted with CH2Cl2
  3. dry with materialThe CH2Cl2 layer was dried over Na2SO4
  4. concentrationconcentrated
  5. customThe crude product was purified by prep-HPLC (C18 column/H2O:MeOH:TFA 90:10:0.1 to 10:90:0.1 gradient)

Quellen und Nachweise

ORD-Eintrag
ord-ec1b5087e30641fbbe332d6bf8cf1b63
Quelldatensatz
uspto-grants-2012_10
Patentnummer
US08278316B2

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