Water → 6-{4-[(3-chloro-5-fluoropyridin-2-yl)oxy]-2-methylphenyl}-1,5-dimethyl-3-{[2-(trimethylsilyl) ethoxy]methyl}pyrimidine-2,4(1H,3H)-dione

HRID 2281929Notes

Reaction equation

HRID 2281929 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[Cl:7][C:8]1[C:9](F)=[N:10][CH:11]=[C:12]([F:14])[CH:13]=1.[OH:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[N:28]([CH3:29])[C:27](=[O:30])[N:26]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[C:25](=[O:39])[C:24]=2[CH3:40])=[C:19]([CH3:41])[CH:18]=1.O>CS(C)=O>[Cl:7][C:8]1[C:9]([O:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]3[N:28]([CH3:29])[C:27](=[O:30])[N:26]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[C:25](=[O:39])[C:24]=3[CH3:40])=[C:19]([CH3:41])[CH:18]=2)=[N:10][CH:11]=[C:12]([F:14])[CH:13]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 193718773-Chloro-2,5-difluoropyridineHCID 1239830176-(4-hydroxy-2-methylphenyl)-1,5-dimethyl-3-{[2-(trimethylsilyl)ethoxy]methyl}pyrimidine-2,4(1H,3H)-dione

Product 1

HCID 1231903836-{4-[(3-chloro-5-fluoropyridin-2-yl)oxy]-2-methylphenyl}-1,5-dimethyl-3-{[2-(trimethylsilyl) ethoxy]methyl}pyrimidine-2,4(1H,3H)-dione

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

Cesium carbonate (476 mg, 1.46 mmol) was added to a mixture of 3-chloro-2,5-difluoropyridine (97%, 150 mg, 0.97 mmol) and C5 (366 mg, 0.972 mmol) in dimethyl sulfoxide (5 mL), and the reaction mixture was stirred at 80° C. for 6 hours. Water was added, and the mixture was extracted three times with ethyl acetate; the combined organic layers were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated in vacuo. Silica gel chromatography (Gradient: 10% to 40% ethyl acetate in heptane) provided the product as a sticky solid. Yield: 414 mg, 0.818 mmol, 84%. 1H NMR (400 MHz, CDCl3) δ 7.96 (d, J=2.7 Hz, 1H), 7.64 (dd, J=7.1, 2.7 Hz, 1H), 7.09-7.15 (m, 3H), 5.51 (AB quartet, JAB=9.3 Hz, ΔνAB=3.4 Hz, 2H), 3.74-3.80 (m, 2H), 3.07 (5, 3H), 2.19 (5, 3H), 1.69 (5, 3H), 1.00-1.06 (m, 2H), 0.03 (5, 9H).

Workup

  1. extractionthe mixture was extracted three times with ethyl acetate
  2. washthe combined organic layers were washed with saturated aqueous sodium chloride solution
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2c4caf4746234b6080a061a61bffec05
Source dataset
uspto-grants-2015_09
Patent number
US09139561B2

Reaction notes

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