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

HRID 2059859ノート

反応式

HRID 2059859 の反応式
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

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 8895Cupric acetate触媒HCID 6344Dichloromethane溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-ec1b5087e30641fbbe332d6bf8cf1b63
出典データセット
uspto-grants-2012_10
特許番号
US08278316B2

反応ノート

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