N,N'-Dimethylethylenediamine → HCID 46927360, compound

HRID 2059864Notes

Reaction equation

HRID 2059864 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:9][C:10]2[N:15]=[CH:14][NH:13][C:12](=[O:16])[CH:11]=2)=[CH:4][CH:3]=1.Br[C:18]1[CH:29]=[CH:28][C:21]([O:22][CH2:23][C:24]([CH3:27])([OH:26])[CH3:25])=[C:20]([O:30][CH3:31])[CH:19]=1.CNCCNC.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.[Cu]I>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:9][C:10]2[N:15]=[CH:14][N:13]([C:18]3[CH:29]=[CH:28][C:21]([O:22][CH2:23][C:24]([OH:26])([CH3:27])[CH3:25])=[C:20]([O:30][CH3:31])[CH:19]=3)[C:12](=[O:16])[CH:11]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 62657Potassium Phosphate, TribasicHCID 595950491-(4-Bromo-2-methoxyphenoxy)-2-methylpropan-2-olHCID 136097745HCID 136097745, compound

Product 1

HCID 46927360HCID 46927360, compoundYield 3.01%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
110 °C

Procedure

A mixture of 6-((4-chlorophenylthio)methyl)pyrimidin-4(3H)-one Part B (25 mg, 0.10 mmol), 1-(4-bromo-2-methoxyphenoxy)-2-methylpropan-2-ol Part B of Procedure 1 (32.7 mg, 0.12 mmol), N1,N2-dimethylethane-1,2-diamine (26.2 mg, 0.30 mmol), potassium phosphate tribasic (63.0 mg, 0.30 mmol) and copper (I) iodide (18.84 mg, 0.10 mmol) in dioxane (4.0 mL) was stirred in a sealed tube at 110° C. for 60 min. After the mixture had cooled to RT, the precipitate removed by filtration and the filtrate was concentrated. The crude product was purified by flash chromatography (silica gel/CH2Cl2-10% MeOH/CH2Cl2 100:0 to 0:100 gradient, using LC-MS to identify fractions containing the desired product). The pure fractions were lyophilized with MeCN/H2O (1:1, 4 mL) to afford the title compound 6-((4-chlorophenylthio)methyl)-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyrimidin-4(3H)-one G-1 as an off-white solid (1.40 mg, 3.01% yield). LC/MS 447 (M+H)+, tR 0.92 min (method 5); 1H NMR (500 MHz, Chloroform-D) δ ppm 8.14 (1H, br. s.), 7.27-7.36 (4H, m), 6.99 (1H, d, J=8.25 Hz), 6.79-6.88 (2H, m), 6.45 (1H, s), 3.96 (2H, s), 3.82-3.90 (5H, m), 1.36 (6H, s).

Workup

  1. temperatureAfter the mixture had cooled to RT
  2. customthe precipitate removed by filtration
  3. concentrationthe filtrate was concentrated
  4. customThe crude product was purified by flash chromatography (silica gel/CH2Cl2-10% MeOH/CH2Cl2 100:0 to 0:100 gradient
  5. additioncontaining the desired product)

Sources & evidence

ORD record
ord-9489f3f26f384777a538aaf344fde102
Source dataset
uspto-grants-2012_10
Patent number
US08278316B2

Reaction notes

Loading…