Potassium Carbonate → methyl 3-[4-[(2,4-difluorobenzyl)oxy]-2-(methylthio)-6-oxopyrimidin-1(6H)-yl]-4-methylbenzoate

HRID 1713204Notes

Reaction equation

HRID 1713204 reaction equation
C(=O)([O-])[O-].[K+].[K+].[F:7][C:8]1[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:9]=1[CH2:10]Br.[OH:17][C:18]1[N:19]=[C:20]([S:36][CH3:37])[N:21]([C:25]2[CH:26]=[C:27]([CH:32]=[CH:33][C:34]=2[CH3:35])[C:28]([O:30][CH3:31])=[O:29])[C:22](=[O:24])[CH:23]=1>>[F:7][C:8]1[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:9]=1[CH2:10][O:17][C:18]1[N:19]=[C:20]([S:36][CH3:37])[N:21]([C:25]2[CH:26]=[C:27]([CH:32]=[CH:33][C:34]=2[CH3:35])[C:28]([O:30][CH3:31])=[O:29])[C:22](=[O:24])[CH:23]=1

Participants

4

Reactant 3

HCID 11430Potassium CarbonateHCID 902971-(Bromomethyl)-2,4-difluorobenzeneHCID 135737355methyl 3-[4-hydroxy-2-(methylthio)-6-oxopyrimidin-1(6H)-yl]-4-methylbenzoate2×

Product 1

HCID 21090186methyl 3-[4-[(2,4-difluorobenzyl)oxy]-2-(methylthio)-6-oxopyrimidin-1(6H)-yl]-4-methylbenzoateYield 64%

Conditions

Temperature
0 °C

Procedure

To a solution of methyl 3-[4-hydroxy-2-(methylthio)-6-oxopyrimidin-1(6H)-yl]-4-methylbenzoate (1.0 g, 0.0033 mol) in DMF (10.0 mL) obtained from step 2, was added potassium carbonate (0.7 g, 0.005 mol) followed by the addition of 2,4 difluorobenzyl bromide (0.8 g, 0.0039 mol) and stirred at 0° C. for 15 min. After stirring at room temperature for 30 min, DMF was distilled in vacuo and the residue was portioned between EtOAc (25 mL) and water (25 mL). The organic phase was washed with water, (2×20 mL), dried (Na2SO4) and concentrated. The resulting material was purified by flash chromatography using EtOAc/hexane (1:1 v/v) to afford the title compound (0.9 g, 64%) as a white powder: 1H NMR (CD3OD/400 MHz) δ 8.08 (dd, 1H, J=8.4 Hz, & 1.6 Hz), 7.83 (d, 1H, J=1.6 Hz), 7.55 (m, 2H), 6.99 (m 2H), 5.64 (s, 1H), 5.48 (s, 2H), 3.89 (s, 3H), 2.50 (s, 3H), and 2.15 (s, 3H); ES-HRMS m/z 433.1016 (M+H calcd for C21H19N2O4SF2 requires 433.1028).

Workup

  1. stirringAfter stirring at room temperature for 30 min
  2. distillationDMF was distilled in vacuo
  3. washThe organic phase was washed with water, (2×20 mL),
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customThe resulting material was purified by flash chromatography

Sources & evidence

ORD record
ord-17e0feaebac64ffcaf88f8516f26cbc2
Source dataset
uspto-grants-2010_09
Patent number
US07795271B2

Reaction notes

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