4-(Dimethoxymethyl)-2-(methylthio)-pyrimidine

a a) a) a Iodomethane ( 128 g, 902 mmol, 1 .20 equiv.) was added carefully to the crude solution of sodium 4-(dimethoxymethyl)pyrimidine-2-thiolate (2) ( 1 56 g, 75 1 mmol) in methanol (700 mL, 1 . 1 M) while maintaining the reaction temperature below 28°C using an ice-water bath for cooling. The resulting mixture was stirred at room temperature for 16 h. After removal of the solvent under reduced pressure, the residue was diluted with water (300 mL) and extracted with ethyl acetate (2 x 150 mL). The combined organic layer was concentrated under reduced pressure and the crude residue purified by passing through a short silica gel pad and washing with diethyl ether (200 mL) to afford 4-(dimethoxymethyl)-2-(methylthio)pyrimidine (3) as a brown oil (53.7 g, 150 g theoretical, 35.7percent). LC-MS m/z 201 (M+ 1 ). Reference: WO20060097341 A 1 , pg 67.4-(dimethoxymethyl)-2-(methylthio)pyrimidine(5): A solution of thiourea (64.7g, 850 mmol, 1.13 equiv.), sodium methanolate (95percent, 40.5 g, 751 mmol, 1.0equiv.) in methanol (500 mL, 1.5 M) was stirred at room temperature for 30 minutes. A solution of (E)-4-(dimethylamino)-1, 1-dimethoxybut-3-en-2-one(4) (130 g, 751 mmol) in methanol (200 mL) was added and the reaction stirred at room temperature for2 h. The crude sodium 4-(dimethoxymethyl)pyrimidine-2-thiolatewas used directlyin the next step without further purification.LC-MSm/z 209 (M+1). Iodomethane (128 g, 902 mmol, 1.20equiv.) was added carefully to the crude solution of sodium 4-(dimethoxymethyl)pyrimidine-2-thiolate (156 g, 751 mmol)in methanol (700 mL, 1.1 M) while maintaining the reaction temperature below 28°C using an ice-water bath for cooling. Theresulting mixture was stirred at room temperature for 16 h. After removal of the solvent under reduced pressure, the residue was diluted with water (300 mL) and extracted with ethylacetate (2 x 150 mL). The combinedorganic layer was concentrated under reduced pressure and the crude residue purifiedby passing through a short silica gel pad and washing with diethyl ether (200mL) to afford 4-(dimethoxymethyl)-2-(methylthio)pyrimidine(5) as a brown oil (53.7 g, 150 g theoretical, 35.7percent). LC-MS m/z201 (M+1).a a a a) Iodomethane ( 128 g, 902 mmol, 1 .20 equiv.) was added carefully to the crude solution of sodium 4-(dimethoxymethyl)pyrimidine-2-thiolate (2) ( 1 56 g, 75 1 mmol) in methanol (700 mL, 1 . 1 M) while maintaining the reaction temperature below 28C using an ice-water bath for cooling. The resulting mixture was stirred at room temperature for 16 h. After removal of the solvent under reduced pressure, the residue was diluted with water (300 mL) and extracted with ethyl acetate (2 x 150 mL). The combined organic layer was concentrated under reduced pressure and the crude residue purified by passing through a short silica gel pad and washing with diethyl ether (200 mL) to afford 4-(dimethoxymethyl)-2-(methylthio)pyrimidine (3) as a brown oil (53.7 g, 150 g theoretical, 35.7%). LC-MS m/z 201 (M+ 1 ). Reference: WO20060097341 A 1 , pg 67.Example 3 4-(dimethoxymethyl)-2-(methylthio)pyrimidine (3): Iodomethane (128 g, 902 mmol, 1.20 equiv.) was added carefully to the crude solution of sodium 4-(dimethoxymethyl)pyrimidine-2-thiolate (2) (156 g, 751 mmol) in methanol (700 mL, 1.1 M) while maintaining the reaction temperature below 28 C. using an ice-water bath for cooling. The resulting mixture was stirred at room temperature for 16 h. After removal of the solvent under reduced pressure, the residue was diluted with water (300 mL) and extracted with ethyl acetate (2×150 mL). The combined organic layer was concentrated under reduced pressure and the crude residue purified by passing through a short silica gel pad and washing with diethyl ether (200 mL) to afford 4-(dimethoxymethyl)-2-(methylthio)pyrimidine (3) as a brown oil (53.7 g, 150 g theoretical, 35.7%). LC-MS m/z 201 (M+1). Reference: WO 2006/0097341A1, pg 67.Iodomethane (128 g, 902 mmol, 1.20 equiv.) was added carefully to the crude solution of sodium 4-(dimethoxymethyl)pyrimidine-2-thiolate (2) (156 g, 751 mmol) in methanol (700 mL, 1.1 M) while maintaining the reaction temperature below 28 C. using an ice-water bath for cooling. The resulting mixture was stirred at room temperature for 16 h. After removal of the solvent under reduced pressure, the residue was diluted with water (300 mL) and extracted with ethyl acetate (2×150 mL). The combined organic layer was concentrated under reduced pressure and the crude residue purified by passing through a short silica gel pad and washing with diethyl ether (200 mL) to afford 4-(dimethoxymethyl)-2-(methylthio)pyrimidine (3) as a brown oil (53.7 g, 150 g theoretical, 35.7%). LC-MS m/z 201 (M+1). Reference: WO 2006/0097341A1 (incorporated by reference), pg 67.4-(dimethoxymethyl)-2-(methylthio)pyrimidine(5): A solution of thiourea (64.7g, 850 mmol, 1.13 equiv.), sodium methanolate (95%, 40.5 g, 751 mmol, 1.0equiv.) in methanol (500 mL, 1.5 M) was stirred at room temperature for 30 minutes. A solution of (E)-4-(dimethylamino)-1, 1-dimethoxybut-3-en-2-one(4) (130 g, 751 mmol) in methanol (200 mL) was added and the reaction stirred at room temperature for2 h. The crude sodium 4-(dimethoxymethyl)pyrimidine-2-thiolatewas used directlyin the next step without further purification.LC-MSm/z 209 (M+1). Iodomethane (128 g, 902 mmol, 1.20equiv.) was added carefully to the crude solution of sodium 4-(dimethoxymethyl)pyrimidine-2-thiolate (156 g, 751 mmol)in methanol (700 mL, 1.1 M) while maintaining the reaction temperature below 28C using an ice-water bath for cooling. Theresulting mixture was stirred at room temperature for 16 h. After removal of the solvent under reduced pressure, the residue was diluted with water (300 mL) and extracted with ethylacetate (2 x 150 mL). The combinedorganic layer was concentrated under reduced pressure and the crude residue purifiedby passing through a short silica gel pad and washing with diethyl ether (200mL) to afford 4-(dimethoxymethyl)-2-(methylthio)pyrimidine(5) as a brown oil (53.7 g, 150 g theoretical, 35.7%). LC-MS m/z201 (M+1).

Molecular Weight:200.26
XLogP3:0.7
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:4
Exact Mass:200.06194880
Monoisotopic Mass:200.06194880
Topological Polar Surface Area:69.5
Heavy Atom Count:13
Complexity:144
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes