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

HRID 2059861Notes

Reaction equation

HRID 2059861 reaction equation
[Cl:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][S:7][C:8]2[CH:13]=[N:12][NH:11][C:10](=[O:14])[CH:9]=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.CO.CC([O-])=O.CC([O-])=O.[Cu+2]>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][S:7][C:8]2[CH:13]=[N:12][N:11]([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:10](=[O:14])[CH:9]=2)=[CH:15][CH:16]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 585798575-(4-chlorobenzylthio)pyridazin-3(2H)-oneHCID 585798634-(2-Hydroxy-2-methylpropoxy)-3-methoxyphenylboronic acid

Product 1

HCID 469272905-(4-chlorobenzylthio)-2-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyridazin-3(2H)-one

Reagents, catalysts & solvents 3

HCID 8895Cupric acetateCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 5-(4-chlorobenzylthio)pyridazin-3(2H)-one Part A (21 mg, 0.083 mmol), 4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenylboronic acid Part D of Procedure 4 (39.9 mg, 0.17 mmol), pyridine (0.067 mL, 0.83 mmol) and Cu(OAc)2 (45.3 mg, 0.25 mmol) in CH2Cl2 (13.0 mL) and MeOH (2.0 mL) was stirred at RT open to air for 4 hours. The mixture was poured into 1.0 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/Water:MeOH:TFA 90:10:0.1 to 10:90:0.1 gradient) giving the title compound 5-(4-chlorobenzylthio)-2-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyridazin-3(2H)-one F-1 (23 mg, 61% yield) as white solid. LC/MS 447 (M+H)+, tR 4.14 min (method 3); 1H NMR (500 MHz, Chloroform-D) δ ppm 7.65 (1H, d, J=2.20 Hz), 7.35 (4H, s), 7.07-7.13 (2H, m), 6.96 (1H, d, J=8.80 Hz), 6.66 (1H, d, J=2.20 Hz), 4.15 (2H, s), 3.81-3.91 (5H, m), 1.35 (6H, s).

Workup

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

Sources & evidence

ORD record
ord-28a10efbe1b74319874bbb2638379e49
Source dataset
uspto-grants-2012_10
Patent number
US08278316B2

Reaction notes

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