Methanol → 6-chloro-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-pyrimidin-4(3H)-one

HRID 2059865

Reaction equation

HRID 2059865 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][NH:5][C:4](=[O:8])[CH:3]=1.[OH:9][C:10]([CH3:25])([CH3:24])[CH2:11][O:12][C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][C:14]=1[O:22][CH3:23].N1C=CC=CC=1.CO>C(Cl)Cl>[Cl:1][C:2]1[N:7]=[CH:6][N:5]([C:16]2[CH:17]=[CH:18][C:13]([O:12][CH2:11][C:10]([OH:9])([CH3:25])[CH3:24])=[C:14]([O:22][CH3:23])[CH:15]=2)[C:4](=[O:8])[CH:3]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 1049Pyridine2×HCID 585798634-(2-Hydroxy-2-methylpropoxy)-3-methoxyphenylboronic acidHCID 1354454786-Chloropyrimidin-4-ol

Product 1

HCID 585799166-chloro-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-pyrimidin-4(3H)-oneYield 46%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 6-chloropyrimidin-4(3H)-one (50 mg, 0.383 mmol), 4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenylboronic acid Part D of Procedure 4 (184 mg, 0.766 mmol), copper (II) acetate, monohydrate (84 mg, 0.421 mmol), and pyridine (1.5 mL, 19.15 mmol) in DCM (4 mL) was stirred at RT under the presence of air overnight (21 hours). Pyridine (0.5 mL) and MeOH (0.5 mL) were added and continued to stir for 2 hours. The reaction was diluted with DCM, washed with 1N HCl, sat NaHCO3, dried (Na2SO4), and concentrated to afford crude product. The crude was purified using ISCO flash chromatography (silica gel/hexanes-ethyl acetate 100:0 to 0:100 gradient) to afford the desired product 6-chloro-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-pyrimidin-4(3H)-one 11A (57.4 mg, 0.177 mmol, 46% yield) as a light brown solid.

Workup

  1. stirringto stir for 2 hours
  2. washwashed with 1N HCl
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customto afford crude product
  6. customThe crude was purified

Sources & evidence

ORD record
ord-7602434f60244de98cdf58296eda172c
Source dataset
uspto-grants-2012_10
Patent number
US08278316B2

Linked notes

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