Methyl iodide → 5-Methyl-2-(methylthio)-4-(thiophen-2-yl)pyrimidine

HRID 507649Notes

Reaction equation

HRID 507649 reaction equation
CN(C)[CH:3]=[C:4]([CH3:12])[C:5]([C:7]1[S:8][CH:9]=[CH:10][CH:11]=1)=O.[NH2:14][C:15]([NH2:17])=[S:16].[CH3:18]C(C)([O-])C.[K+].IC>C(O)(C)C.CC(O)(C)C>[CH3:12][C:4]1[C:5]([C:7]2[S:8][CH:9]=[CH:10][CH:11]=2)=[N:14][C:15]([S:16][CH3:18])=[N:17][CH:3]=1

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 2723790ThioureaHCID 23665647Potassium tert-butoxideHCID 684666763-(Dimethylamino)-2-methyl-1-(2-thienyl)-2-propen-1-one

Product 1

HCID 574288625-Methyl-2-(methylthio)-4-(thiophen-2-yl)pyrimidine

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6386tert-ButanolSolvent

Procedure

3-(Dimethylamino)-2-methyl-1-(thiophen-2-yl)prop-2-en-1-one (0.2 g, 1.02 mmol) was dissolved in isopropyl alcohol (2mL) at room temperature. Thiourea (0.077 g, 1.02 mmol) followed by potassium tert-butoxide (1.102 mL of a 1.0 M solution in 2-methyl-2-propanol) was added to the mixture, which was then heated to reflux overnight. The reaction was cooled down to rt and iodomethane (0.126 mL, 2.04 mmol) was added to the reaction, which was stirred for an additional 6 h. The volatiles were removed in vacuo and the residue was dissolved in ethyl acetate, washed with saturated aqueous sodium bicarbonate, water and brine. The organic layer was then dried with sodium sulfate, concentrated in vacuo and purified by flash chromatography using a gradient of 5 to 30% ethyl acetate in hexanes. The pure fractions yielded a tan solid (0.15 g). MS (M+H)+ 223.

Workup

  1. additionwas added to the mixture, which
  2. temperaturewas then heated
  3. temperatureto reflux overnight
  4. customThe volatiles were removed in vacuo
  5. dissolutionthe residue was dissolved in ethyl acetate
  6. washwashed with saturated aqueous sodium bicarbonate, water and brine
  7. dry with materialThe organic layer was then dried with sodium sulfate
  8. concentrationconcentrated in vacuo
  9. custompurified by flash chromatography

Sources & evidence

ORD record
ord-4c8eaee8984a4f71adfadef6b9b1cdcd
Source dataset
uspto-grants-2010_08
Patent number
US07786132B2

Reaction notes

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