N,N'-Dimethylethylenediamine → 4-(4-chlorobenzylthio)-1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyrimidin-2(1H)-one

HRID 2059844Notes

Reaction equation

HRID 2059844 reaction equation
CNCCNC.Br[C:8]1[CH:19]=[CH:18][C:11]([O:12][CH2:13][C:14]([CH3:17])([OH:16])[CH3:15])=[C:10]([O:20][CH3:21])[CH:9]=1.[Cl:22][C:23]1[CH:37]=[CH:36][C:26]([CH2:27][S:28][C:29]2[CH:34]=[CH:33][NH:32][C:31](=[O:35])[N:30]=2)=[CH:25][CH:24]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.C(Cl)Cl.[Cu]I>[Cl:22][C:23]1[CH:37]=[CH:36][C:26]([CH2:27][S:28][C:29]2[CH:34]=[CH:33][N:32]([C:8]3[CH:19]=[CH:18][C:11]([O:12][CH2:13][C:14]([OH:16])([CH3:17])[CH3:15])=[C:10]([O:20][CH3:21])[CH:9]=3)[C:31](=[O:35])[N:30]=2)=[CH:25][CH:24]=1

Participants

8

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 62657Potassium Phosphate, TribasicHCID 595950491-(4-Bromo-2-methoxyphenoxy)-2-methylpropan-2-olHCID 1785185414-(4-chlorobenzylthio)pyrimidin-2(1H)-one

Product 1

HCID 469268044-(4-chlorobenzylthio)-1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyrimidin-2(1H)-oneYield 7%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

N1,N2-dimethylethane-1,2-diamine (356 mg, 4.04 mmol) was added to a stirred mixture of 1-(4-bromo-2-methoxyphenoxy)-2-methylpropan-2-ol Part 1B of Procedure 1 (222 mg, 0.807 mmol), 4-(4-chlorobenzylthio)pyrimidin-2(1H)-one Part A (170 mg, 0.67 mmol), copper(I) iodide (77 mg, 0.404 mmol) and potassium phosphate, tribasic (857 mg, 4.04 mmol) in dioxane (8 mL). The mixture was stirred at 105° C. for 7 h. The reaction mixture was diluted with methylene chloride, washed with saturated sodium bicarbonate, dried (MgSO4) and concentrated. The crude product was subjected to ISCO flash chromatography (silica gel/hexane-EtOAc 100:0 to 0:100 gradient, used LC/MS to identify fractions containing the desired product) to afford the title compound 4-(4-chlorobenzylthio)-1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyrimidin-2(1H)-one A-1 (22 mg, 0.048 mmol, 7% yield, eluted with 100% EtOAc) as a pale gummy solid.

Workup

  1. washwashed with saturated sodium bicarbonate
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated
  4. additioncontaining the desired product)

Sources & evidence

ORD record
ord-b22015f9ca9643368105e36ca5acd36c
Source dataset
uspto-grants-2012_10
Patent number
US08278316B2

Reaction notes

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