Hydrochloric Acid → HCID 46927357, compound

HRID 2059856Notes

Reaction equation

HRID 2059856 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:9][C:10]2[CH:15]=[N:14][NH:13][C:12](=[O:16])[CH:11]=2)=[CH:4][CH:3]=1.[OH:17][C:18]([CH3:33])([CH3:32])[CH2:19][O:20][C:21]1[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][C:22]=1[O:30][CH3:31].N1C=CC=CC=1.Cl>C(Cl)Cl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:9][C:10]2[CH:15]=[N:14][N:13]([C:24]3[CH:25]=[CH:26][C:21]([O:20][CH2:19][C:18]([OH:17])([CH3:33])[CH3:32])=[C:22]([O:30][CH3:31])[CH:23]=3)[C:12](=[O:16])[CH:11]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 585798634-(2-Hydroxy-2-methylpropoxy)-3-methoxyphenylboronic acidHCID 58579905HCID 58579905, compound

Product 1

HCID 46927357HCID 46927357, compound

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

To a mixture of 5-((4-chlorophenylthio)methyl)pyridazin-3(2H)-one Part D (60 mg, 0.24 mmol), copper(II) acetate (95 mg, 0.48 mmol), and 4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenylboronic acid Part D of Procedure 4 (114 mg, 0.48 mmol) in CH2Cl2 (20 mL) stirring at RT open to air was added pyridine (1.92 mL, 23.74 mmol) in portions over 4 hours. 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 subjected to flash chromatography (silica gel/hexane-EtOAc 100:0 to 0:100 gradient, using LC-MS to identify fractions containing the desired product). This material was further purified by preparative HPLC (C18 column/Water:MeOH:TFA 90:10:0.1 to 10:90:0.1 gradient). The clean fractions were lyophilized using MeCN/H2O (1:1, 10 mL) to obtain the title compound 5-((4-chlorophenylthio)methyl)-2-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyridazin-3(2H)-one E-1 (57 mg, 53% yield) as white solid. LC/MS 447 (M+H)+, tR 0.95 min (method 5); 1H NMR (400 MHz, Chloroform-D) δ ppm 7.85 (1H, d, J=2.26 Hz), 7.30 (4H, s), 7.09-7.14 (2H, m), 6.96 (1H, d, J=9.29 Hz), 6.68-6.72 (1H, m), 3.87 (7H, t, J=5.40 Hz), 1.35 (6H, s).

Workup

  1. extractionextracted with CH2Cl2
  2. dry with materialThe CH2Cl2 layer was dried over Na2SO4
  3. concentrationconcentrated
  4. additioncontaining the desired product)
  5. customThis material was further purified by preparative HPLC (C18 column/Water:MeOH:TFA 90:10:0.1 to 10:90:0.1 gradient)

Sources & evidence

ORD record
ord-779ef95aa0c14b5e95c833735f24ff47
Source dataset
uspto-grants-2012_10
Patent number
US08278316B2

Reaction notes

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